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 > or = 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).

Thermal pain thresholds are decreased in the migraine preattack phase.

BACKGROUND AND PURPOSE: Migraine patients may have cutaneous allodynia during attacks. In order to investigate if pain physiology changes in the preattack phase we estimated heat pain and cold pain detection threshold (HPT and CPT) on three different days in 41 migraine patients and 28 controls. METHODS: A thermode was applied at four sites bilaterally: forehead, face, neck, and hand. A subgroup of 11 migraine patients had been tested within 24 h before their next attack and in the interictal phase. RESULTS: In the preattack phase, HPT was lower compared with the paired interictal recording for the hand (44.8 degrees C vs. 45.9 degrees C, P = 0.009), neck (46.8 degrees C vs. 48.2 degrees C, P = 0.02), and forehead (45.1 degrees C vs. 46.3 degrees C, P = 0.02). Neck and hand CPT were higher in the preattack phase than interictally (10 degrees C vs. 7.3 degrees C, P = 0.01 and 11.6 degrees C vs. 9.4 degrees C, P = 0.06, respectively). Preattack forehead changes were most apparent on the headache side of the subsequent attack. DISCUSSION: Subclinical preattack thermal pain hypersensitivity seems to be a feature of the process that leads to a migraine attack.

Pain induced by low-grade stress in patients with fibromyalgia and chronic shoulder/neck pain, relation to surface electromyography.

The mechanisms of pain causation in fibromyalgia (FMS) and chronic shoulder/neck pain (SNP) are still debated. We wanted to compare muscle activity and pain development during and after low-grade mental stress in FMS and SNP patients. Twenty-three women with FMS, 29 women with chronic SNP and 35 healthy women performed a stressful task lasting 60 min followed by a 30 min recovery period. We recorded surface electromyography over the trapezius, neck, temporalis and frontalis muscles. Subjects reported their pain at the corresponding locations together with the development of fatigue and perceived tension. Significant differences between FMS and SNP groups were not observed either for muscular or subjective responses. SNP patients and controls responded with more pain in the trapezius and neck regions than in the forehead, in contrast to FMS patients who had a more generalized pain response. Development of pain, tension and fatigue was not related to muscle activity for any group. We conclude that FMS and SNP patients have similar pain and electromyographic responses. The results suggest that similar pathophysiological mechanisms are involved although the responses are more generalised in FMS than in SNP patients. Muscular activity did not explain the pain which developed during the stressful task for either group. Pain lasted longer during recovery in both FMS and SNP patients compared to healthy controls, possibly a result of disease-related sensitisation in pain pathways.

Headache and transient focal neurological symptoms during pregnancy, a prospective cohort.

OBJECTIVE: The main purpose of the present prospective study was to evaluate the course of migraine and non-migrainous headache during pregnancy and to estimate the occurrence of self-reported transient focal neurological symptoms. MATERIAL AND METHODS: In total 1631 (77%) pregnant women completed the study and were followed-up during pregnancy. The first questionnaire (Q1) was sent together with the appointment letter and delivered at the time of ultrasound screening. The second questionnaire (Q2), to be filled in during pregnancy, was delivered at the time of birth. Q1 and Q2 covered questions about headache, transient neurological symptoms, and other background and demographic data. Subjects reporting transient sensory, motor or visual disturbances were also interviewed by phone in order to achieve a more precise description of the symptoms. RESULTS: A total of 58% subjects with migraine reported not having migraine or no headache at all during pregnancy. Among individuals with non-migrainous headache 25% reported not having any headaches, while 1.9% of the subjects without headache experienced headache attacks during pregnancy that fulfilled the criteria for migraine. Individuals without headache or with non-migrainous headache reported significantly less sensory, motor and visual disturbances during pregnancy compared with migraine subjects. More than 60% of those with possible aura phenomenon were migraine patients, while symptoms of peripheral or non-neurological origin were more common among headache free or those with non-migrainous headache. CONCLUSION: Transient neurological symptoms were less common among individuals without or with non-migrainous headache compared with migraine. This may indicate that there is an increased susceptibility of unknown cause for these symptoms among migraine patients during pregnancy.

Radiofrequency denervation of facet joints C2-C6 in cervicogenic headache: a randomized, double-blind, sham-controlled study.

Cervicogenic headache is still a controversial disease entity, and good and reliable treatment is lacking. In the present randomized, sham-controlled, patient- and evaluator-blinded study, 12 patients with a disabling, long-standing and treatment-resistant strictly unilateral cervicogenic headache were included. The diagnosis was based on purely clinical criteria. Six were randomized to receive radiofrequency neurotomy of facet joints C2-C6 ipsilateral to the pain, and six were randomized to sham treatment. Patients were followed for 2 years with diary registration of pain for 14-days periods after 1, 3, 6, 12, 18 and 24 months, and also followed with algometry and neck mobility measurements at 3, 12 and 24 months. Side-effects were minor and short-lasting, and those patients who were treated with neurotomy were somewhat improved at 3 months, but later there were no marked differences between the groups. In conclusion, the procedure is probably not beneficial in cervicogenic headache.

A randomized, double blind study of the prophylactic effect of hyperbaric oxygen therapy on migraine.

In a double blind, placebo-controlled study to assess the prophylactic effect of hyperbaric oxygen therapy on migraine, 40 patients were randomly assigned to a treatment group receiving three sessions of hyperbaric oxygen, or a control group receiving three hyperbaric air treatments. The patients were instructed to keep a standardized migraine diary for eight weeks before and after the treatment. Thirty-four patients completed the study. Our primary measure of efficacy was the difference between pre- and post-treatment hours of headache per week. The results show a nonsignificant reduction in hours of headache for the hyperbaric oxygen group compared to the control group. Levels of endothelin-1 in venous blood before and after treatment did not reveal any difference between the hyperbaric oxygen and control groups. We conclude that the tested protocol does not show a significant prophylactic effect on migraine and does not influence the level of endothelin-1 in venous blood.

Clinical utility of EEG in alcohol-related seizures.

OBJECTIVE: To study if electroencephalogram (EEG) can discriminate between alcohol-related seizures (ARS) and seizures unrelated to alcohol use. MATERIAL AND METHODS: Alcohol-related seizures was defined as a seizure in a patient with score > or = 8 in the Alcohol Use Disorders Identification Test (AUDIT). Twenty-seven patients with ARS (22 without epilepsy: ARSwE), 21 AUDIT-negative epileptic patients with seizures (ES), and 30 other AUDIT negative patients with seizures (OS) were studied. Thirty-seven epilepsy outpatients and 79 sciatica inpatients were controls. RESULTS: Epileptiform and slow activity were less frequent in the ARSwE than in the ES group. Alpha amplitude was lower in the ARSwE than the other groups. Photoparoxysmal activity was not observed. EEG was associated with a larger negative predictive value (78% probability of non-ARS if EEG was abnormal) than a positive predictive value (55% probability of ARS if EEG was normal). CONCLUSION: A definitely abnormal EEG suggests epilepsy or symptomatic seizures unrelated to alcohol. The predictive value of a normal EEG is limited, but the typical post-ictal finding in ARS is nevertheless a normal low-amplitude EEG record.

Detection of alcohol abuse in neurological patients: variables of clinical relevance to the accuracy of the %CDT-TIA and CDTect methods.

OBJECTIVES: Alcohol-related neurological diseases are encountered frequently. Early diagnosis is essential, because minimal intervention effectively reduces hazardous alcohol consumption and may prevent permanent neurological damage. Carbohydrate-deficient transferrin (CDT) is a valuable tool for the identification of alcohol abuse, but for unselected patient populations, reduced test accuracy has been reported. Recently, factors other than alcohol use have been shown to influence CDT levels. Our aim was to identify clinically relevant factors that might reduce test accuracy. MATERIAL AND METHODS: We included 397 neurological patients consecutively hospitalized for seizures, ischemic stroke, or sciatica and 87 patients who attended routine outpatient controls for epilepsy. Blood samples were analyzed for CDT by using two commercially available tests, %CDT-TIA and CDTect. All patients underwent a semistructured clinical interview that included a record of the reported ethanol consumption during the last 8 days, and all completed the Alcohol Use Disorders Identification Test (AUDIT). Current medication, medical history, and demographic information also were obtained. RESULTS: Both tests were elevated in female antiepileptic drug users, compared with others who reported no recent ethanol intake. A higher number of false-positive cases was seen for CDTect than for %CDT. Various combinations of CDT and gamma-glutamyltransferase improved sensitivity, but at the cost of reduced specificity. Variables that predicted the variation of CDT included antiepileptic drug use, sex, body mass index, and smoking. Total transferrin levels were reduced significantly in postmenopausal women, whereas a falling trend was seen for CDTect. Transferrin alterations caused a higher number of false-positive results for CDTect than for %CDT. The area under the receiver operating characteristics curve for women was higher for CDTect than for %CDT, and for %CDT, the area under the receiver operating characteristics curve was higher for men than for women. CONCLUSION: The accuracy of CDT for detection of alcohol abuse in neurological patients was generally low, particularly for women. Combination variables of CDT and gamma-glutamyltransferase did not increase test accuracy. Variables that were associated with higher CDT levels included female sex, antiepileptic drug use, transferrin alterations, and possibly low body mass index. When factors known to cause poor accuracy in particular patient groups are appreciated, CDT may be a good adjunct to the clinical examination.

Prophylactic treatment of migraine with angiotensin converting enzyme inhibitor (lisinopril): randomised, placebo controlled, crossover study.

OBJECTIVE: To determine the efficacy of an angiotensin converting enzyme inhibitor in the prophylaxis of migraine. DESIGN: Double blind, placebo controlled, crossover study. SETTING: Neurological outpatient clinic. PARTICIPANTS: Sixty patients aged 19-59 years with migraine with two to six episodes a month. INTERVENTIONS: Treatment period of 12 weeks with one 10 mg lisinopril tablet once daily for one week then two 10 mg lisinopril tablets once daily for 11 weeks, followed by a two week wash out period. Second treatment period of one placebo tablet once daily for one week and then two placebo tablets for 11 weeks. Thirty participants followed this schedule, and 30 received placebo followed by lisinopril. MAIN OUTCOME MEASURES: Primary end points: number of hours with headache, number of days with headache, number of days with migraine. Secondary end points: headache severity index, use of drugs for symptomatic relief, quality of life and number of days taken as sick leave, acceptability of treatment. RESULTS: In the 47 participants with complete data, hours with headache, days with headache, days with migraine, and headache severity index were significantly reduced by 20% (95% confidence interval 5% to 36%), 17% (5% to 30%), 21% (9% to 34%), and 20% (3% to 37%), respectively, with lisinopril compared with placebo. Days with migraine were reduced by at least 50% in 14 participants for active treatment versus placebo and 17 patients for active treatment versus run-in period. Days with migraine were fewer by at least 50% in 14 participants for active treatment versus placebo. Intention to treat analysis of data from 55 patients supported the differences in favour of lisinopril for the primary end points. CONCLUSION: The angiotensin converting enzyme inhibitor, lisinopril, has a clinically important prophylactic effect in migraine.

Weekday distribution of alcohol consumption in Norway: influence on the occurrence of epileptic seizures and stroke?

Binge drinking at weekends is considered to be a predominant feature of alcohol consumption in the Nordic countries. Neurological diseases, such as seizures and stroke, have been reported to occur in temporal relation to alcohol intoxication and withdrawal. We wanted to investigate weekday variances in alcohol consumption in relation to the onset of neurological symptoms in these disorders. Consecutive patients admitted for epileptic seizures (n = 142) and ischemic strokes (n = 91) were included in the study. Control groups were consecutively hospitalized sciatica patients (n = 181), outpatients with epilepsy (n = 91), and healthy subjects (n = 254). The day-by-day alcohol intake during the 8 days prior to hospital admission was recorded. Seizures occurring in subjects with hazardous alcohol consumption, operationally defined by a score > or =8 in the Alcohol Use Disorders Identification Test (AUDIT-positive) were considered to be related to alcohol use. Binge drinkers were identified by an alcohol intake, on at least 1 of the last 3 days, of > or =6 standard units in men, or > or =4 standard units in women. Thirty-five percent of seizure patients were AUDIT-positive, in contrast to 18% and 16% of stroke and sciatica patients, and 12% and 13% of epilepsy outpatients and healthy controls. Twenty-three percent of seizure patients were binge drinkers whereas in the other groups, this proportion did not exceed 10%. In all groups, alcohol consumption peaked on Saturdays. More seizures occurred on Mondays compared to Saturdays, with a diminishing trend through the week. However, AUDIT-negative seizure patients, of which binge drinking occurred in only 5%, caused this difference. AUDIT-positive seizure patients had a higher and more evenly distributed alcohol intake through the week, and the occurrence of seizures in this group did not differ significantly between days of the week. Alcohol consumption peaked 2 days prior to the onset of withdrawal seizures. The weekend drinking pattern was confirmed for all the study groups. Hazardous alcohol consumption preceded every third acute seizure, but was found in only one of eight outpatients with epilepsy. AUDIT-negative patients caused a peak of seizure admissions on Mondays, compared to Saturdays, with a diminishing trend through the week.

The diversity of seizures related to alcohol use. A study of consecutive patients.

The aim of this study was to investigate the influence of hazardous alcohol drinking on the occurrence of epileptic seizures, the semiology of such seizures, and the extent of the problem. A consecutive sample of 142 acute seizure patients (78 male and 64 female, mean age 46 (16-79) years) was studied. Control groups were 185 consecutive sciatica patients and 254 healthy individuals. Subjects with a hazardous alcohol drinking level were identified by a score >8 in the Alcohol Use Disorders Identification Test (AUDIT). Seizures in AUDIT-positive individuals occurring within 72 h of the last drink were considered to be related to alcohol withdrawal. Generalized or partial onset seizures were classified on the basis of history, electroencephalographic (EEG) and neuroradiological findings. Thirty-five percent of seizure patients were AUDIT-positive, whereas conversely 27% were abstainers. Two-thirds of AUDIT-positive seizure patients met the criteria for withdrawal seizures. Indications of partial onset seizures were found in 25 (51%) of AUDIT-positive patients, all secondarily generalized seizures. Sixty percent of generalized onset seizure patients were AUDIT-positive. In conclusion, seizure patients included significantly more AUDIT-positive subjects, as well as abstainers, than healthy Norwegian controls and consecutive sciatica patients from our hospital. Partial onset seizures are more frequent among hazardous drinkers than hitherto recognized. A generalized onset seizure in adults warrants a high suspicion of alcohol as a provoking factor. Routine screening of acute seizure admissions with the Alcohol Use Disorders Identification Test is recommended.

The reproducibility of cephalic pain pressure thresholds in control subjects and headache patients.

Pain pressure thresholds (PPT) were measured at 13 cephalic points bilaterally in 30 headache patients (10 with tension-type headache, 10 with migraine and 10 with cervicogenic headache) and 10 control subjects on three different days. During the sessions, the subjects reported their pain intensity on the right and left sides of the head on a visual analogue scale (VAS). The variability between days was estimated as a coefficient of repeatability (CR = 2 standard deviations of intraindividual differences). The mean CR across all 13 locations was larger in headache patients (2.0 kg/cm2) than in controls (1.68 kg/cm2). Variability (CR) was larger in headache patients as compared to control subjects for 11 of the 13 points (p = 0.02). Reliability was better in controls (intraclass correlation coefficients (ICC) ranging from 0.55 to 0.85) than in headache patients (ICC ranging from 0.43 to 0.78). A moderate negative association between PPT and pain intensity was demonstrated. The intraindividual PPT difference (PPT on the most painful occasions-PPT on the least painful occasions) was negative at 12 of 13 cephalic points (p = 0.003, across-location mean difference: -0.20 kg/cm2). The PPT differed significantly from one day to the next. A part of this variation was presumably related to the circumstances around the procedure; thresholds were lower when the subjects came directly to algometry without any preceding medical examination at all 13 points (p = 0.0002). These results have implications for the planning of future algometer studies. The sample size that is required in studies of headache patients is greater than that in studies of healthy subjects, especially when patients suffer from pain during the PPT session. Particular attention should be paid to circumstances (e.g. preceding medical investigations) around the algometry procedure in order to reduce variability.

Idiopathic normal pressure hydrocephalus: the CSF tap-test may predict the clinical response to shunting.

A follow-up study was performed in nine patients with idiopathic normal pressure hydrocephalus (NPH) 37 months (mean) after shunting and 10 non-operated controls with comparable degrees of ventricular enlargement, gait disorder, and dementia. Five operated patients vs. no controls reported sustained general improvement (p < 0.02). Objectively improved gait at follow-up (compared with preoperative status) was found in five of the six tested NPH-patients vs. none of the controls (p < 0.005). Improved gait and/or psychometric function was found in four of six NPH vs. none of eight control patients (p < 0.02) after drainage of 40 ml cerebrospinal fluid (CSF tap-test). Improved gait during the CSF tap-test predicted continued improvement at follow-up. Temporal horn size was the only radiological variable which showed a (moderate) positive correlation with resistance to CSF absorption and rate of pressure increase. The size of the third ventricle diminished in parallel with clinical improvement.

Intracutaneous sterile water injections do not relieve pain in cervicogenic headache.

Intracutaneous sterile water injections have been reported to relieve acute labor pain and cervical pain in whip-lash patients. A double blind cross-over trial has presently been conducted in 10 women with cervicogenic headache in order to investigate whether sterile water injections were effective in this disorder. No benefit was observed for either treatment (isotonic saline or sterile water), neither on pain during the first 14 days nor on neck mobility. We conclude that intracutaneous sterile water injections is not effective in cervicogenic headache.