Cerebrospinal fluid cytokine levels in migraine, tension-type headache and cervicogenic headache.

Cytokines have been measured in cerebrospinal fluid (CSF) from headache patients [infrequent episodic tension-type headache (TTH) and migraine with or without aura, all during attack, and cervicogenic headache] and compared with levels in pain-free individuals. Both proinflammatory [interleukin (IL)-1beta, tumour necrosis factor-alpha and monocyte chemoattractant protein-1 (MCP-1)] and anti-inflammatory cytokines [IL-1 receptor antagonist (IL-1ra), IL-4, IL-10 and transforming growth factor-beta1 (TGF-beta1)] were included. There were significant group differences in IL-1ra, TGF-beta1 and MCP-1 in episodic TTH and migraine compared with controls, and a significant difference in MCP-1 between cervicogenic headache and migraine with aura. Intrathecal MCP-1 correlated with IL-1ra, IL-10 and TGF-beta1 in episodic TTH, and MCP-1 with IL-10 in migraine with aura. Cytokine increases were modest compared with those often accompanying serious neurological conditions, and may represent a mild response to pain. We believe this to be the first comparative study of CSF cytokine levels in connection with headache.

Examination of the diagnostic validity of 'headache attributed to whiplash injury': a controlled, prospective study.

Acute and chronic headache attributed to whiplash injury are new diagnostic entities in the International Classification of Headache Disorders, second edition. A main objective of the present study was to assess the validity of these nosologic entities by studying the headache pattern in an inception cohort of 210 rear-end car collision victims and in 210 matched controls. Consecutive drivers involved in rear-end collisions were identified from the daily records of the Traffic Police Department of Kaunas, Lithuania. A standard self-report questionnaire was sent to the drivers between 2 and 7 days after the collision, and their passengers were recruited as well. Headache and neck pain were evaluated within 7 days of the collision, at 2 months and 1 year after the collision. A control group of non-traumatized subjects received questionnaires at the time of the selection and 1 year later. Of the 75 collision victims who developed headache within the first 7 days of the collision, 37 had a clinical picture in accordance with the criteria for acute whiplash headache (i.e., concomitant neck pain) and 38 did not. For acute headache after collision, concomitant neck pain was of no relevance to the headache type or its course. In both these subgroups, migraine and tension-type headache could be diagnosed in similar proportions and the prognosis after 2 months and 1 year was also similar. Preexisting headache was a strong prognostic factor in both groups for both acute and chronic pain. Compared with the non-traumatized control group, the 1-year incidence of new or worsened headache, or of headache improvement, was the same. A likely interpretation of the data is that acute headaches after rear-end car collisions mainly represent episodes of a primary headache precipitated by the stress of the situation. We conclude that the nosologic validity of both acute and chronic whiplash headache is poor as the headaches, in accordance with the criteria lack distinguishing clinical features and have the same prognosis compared with headaches in a control group.

Progressive central and peripheral demyelinating disease of adult onset in a Norwegian family.

OBJECTIVE: To describe the clinical features of a Norwegian family with a combined central and peripheral demyelinating disease. DESIGN: Multiple case report. SUBJECTS AND MATERIALS: Three generations of a Norwegian family. Medical records were available for all 9 members of the second generation and 5 affected members in the third generation. RESULTS: At least 5 members had clinical features, neuroimaging findings, and electrophysiologic signs indicating a chronic progressive disorder affecting both the central and peripheral nervous systems. The clinical symptoms developed between the ages of 30 and 70 years in affected family members, who gradually developed sensory loss, muscle deterioration, and distal weakness in all extremities, unsteady gait, and dysarthria. Five of 9 persons in the second generation had strokes and experienced mental deterioration. The initial stroke episodes were recognized between the ages of 54 and 68 years, and death occurred between the ages of 62 and 75 years. In 7 subjects, cerebrospinal fluid protein levels were increased, and in 5 agar gel electrophoresis indicated blood-brain barrier dysfunction. Seven family members had neuroimaging signs of a widespread white matter disorder. In 4 subjects, neurophysiological investigations indicated a polyneuropathy, and in 3 subjects, results from a sural nerve biopsy showed a demyelinating neuropathy. There was no evidence of co-inheritance with genetic markers of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (19p), PMP22 (17q), APP (21q), CMTX1 (Xq), or PLP (Xq). CONCLUSIONS: Progressive central and peripheral demyelinating disease seems to be a distinct type of hereditary adult-onset demyelinating disorder affecting both the peripheral and central nervous systems. Its exact nature remains unknown.

Interleukin-1beta potentiates endothelin ET(B) receptor-mediated contraction in cultured segments of human temporal artery.

Segments of human temporal artery were placed in organ culture for up to 4 days and examined for endothelin ET(B) receptor activity in the presence and absence of the pro-inflammatory cytokine interleukin-1beta (IL-1beta) by in vitro pharmacology and reverse transcriptase-polymerase chain reaction (RT-PCR). The contractile effect of prostaglandin F2alpha (used as a reference), was not significantly altered by culture or IL-1beta. However, the selective ET(B) agonist sarafotoxin S6c induced no contraction in fresh arteries, but marked contraction after culture. Both maximal contraction and potency to sarafotoxin S6c were increased in segments incubated with IL-1beta . The contraction was sensitive to BQ 788 (ET(B) antagonist), but not FR 139317 (ET(A) antagonist). Actinomycin D abolished the contraction, whereas only the cytokine-induced increase in contraction was inhibited by cycloheximide. ET(A) and ET(B) receptor mRNAs were detected in all arteries; predominantly for the ET(A) receptor in fresh arteries, and for the ET(B) receptor after culture. However, there was no change in the ET(A)/ET(B) receptor mRNA ratio after treatment with IL-1beta. This suggests de novo synthesis of contractile ET(B) receptors after organ culture and that IL- 1beta may further stimulate translation of the mRNA to active receptors. The results raise the possibility that contractile ET(B) receptors may be implicated in disease states with inflammatory processes.

The prevalence of delayed and advanced sleep phase syndromes.

To determine the prevalence of the delayed sleep phase syndrome (DSPS) and the contrasting advanced sleep phase syndrome (ASPS), a cross-sectional nationwide epidemiological study was performed in Norway. Screening questionnaires were sent to a random sample of 10,000 adult individuals (18-67 y), of both sexes, taken from the National register of Norway. The response rate was 77%. Diagnoses of DSPS and ASPS were based on International Classification of Sleep Disorders (ICSD) criteria. All individuals suspected of having DSPS or ASPS were requested to fill out a second questionnaire, and a sleep log for four weeks. Subjects for whom the suspicion of DSPS or ASPS could be upheld were contacted by telephone for a final confirmation. Of the 129 possible DSPS cases identified from the screening questionnaires, 17 (9 f; 8 m) remained with the confirmed diagnosis of DSPS. The prevalence was calculated to be 0.17% (95% Confidence Intervals: 0.10-0.28). Thirteen individuals had a mild to moderate DSPS and four had a severe DSPS. The mean age of onset was 15.4 y, and mean duration was 19.2 y. There was no significant correlation between prevalence and age. A sleep phase delay (MSPD) induced by social/environmental or psychological factors was found in 55 subjects (prevalence = 0.72%). Using strict ICSD criteria, no case of ASPS was detected, confirming earlier assumptions of the extreme rarity of this condition.

Neck pain in the general population.

STUDY DESIGN: A randomized cross-sectional questionnaire was used to determine the prevalence of neck pain in Norwegian adults. OBJECTIVES: The frequency and duration of neck pain were assessed. SUMMARY OF BACKGROUND DATA: Reliable epidemiologic studies on the prevalence of neck pain in the general population have been sparse. METHODS: A questionnaire that inquired about neck pain within the last year was sent to a random sample of 10,000 adult Norwegians. RESULTS: Overall, 34.4% of the responders had experienced neck pain within the last year. A total of 13.8% reported neck pain that lasted for more than 6 months. CONCLUSIONS: Chronic neck pain is a frequent symptom in the general population, particularly in women. Although reservations have to be taken as to the interpretation, the reported prevalence of persisting pain after whiplash injuries is of the same magnitude as the prevalence of chronic neck pain in the general population.

Extracranial nerves in the posterior part of the head. Anatomic variations and their possible clinical significance.

STUDY DESIGN: An anatomic study of the peripheral nerves innervating the occipital region. OBJECTIVES: To study the topography of the extracranial occipital nerves, to define optimal locations for anesthetic nerve blockades, to provide guidelines to use with the suboccipital surgical approach, and to search for structures with putative pathogenetic implications in cases of unilateral headache. SUMMARY OF BACKGROUND DATA: There is little consensus in the literature concerning the sensory innervation of the scalp. Previous clinical and morphologic studies have not proven the existence of an entrapment mechanism in cases of unilateral head pain. Specific sites for anesthetic blockades have been defined only partly with reference to topographic landmarks. METHODS: The topography of the greater occipital (n = 20), the minor occipital (n = 19), and the greater auricular nerves (n = 17) was studied by dissection of 10 embalmed cadavers. Measurements of internerve distances and distances to defined landmarks were supplemented by drawings and photographs. RESULTS: A great variability in nerve topography was seen interindividually and intraindividually. The greater occipital nerve ascended between 5 mm and 28 mm from the midline along the intermastoid line. The minor occipital nerve was found between 32 mm and 90 mm from the midline along the same landmark. In most cases, both the greater occipital nerve and the minor occipital nerve pierced the aponeurosis after branching. Thirteen greater occipital nerves and eight minor occipital nerves also were embedded in this tissue. Twelve of the 20 greater occipital nerves formed a rich network around the occipital artery. However, anatomic structures with an imminent risk of causing entrapment were not observed. CONCLUSION: The results of this study suggest that optimal locations for blockade techniques should be reconsidered. The acquired knowledge concerning greater auricular and minor occipital nerves behind the sternocleidomastoid muscle may aid in preventing intraoperative injuries.

Topographic variations in the peripheral course of the greater occipital nerve. Autopsy study with clinical correlations.

The description of the peripheral course of the greater occipital nerve (GON) varies in the literature. An autopsy study was done on 20 cases without known headache problems. These findings showed a marked variation in the relation between the GON and nuchal muscles. The trapezius muscle was penetrated by the GON in 45% of cases, the semispinal muscle of the head was penetrated in 90% of cases, and the inferior oblique muscle of head was penetrated in 7.5% of cases. Macroscopic findings of possible compression were made in 11 cases (27.5%), indicating that nerve compression per se may be of minor importance since it seems to exist in the absence of headache.

Cervicogenic headache. The differentiation from common migraine. An overview.

Common migraine and cervicogenic headache have many traits in common, so many that they may be mixed up. Both are unilateral headaches with a female preponderance. However, as for a number of variables, they differ. This first and foremost has to do with factors concerning the neck. In cervicogenic headache, the following symptoms and signs are present: a reduced range of motion in the neck; mechanical precipitation of attack, either by neck movements or by external pressure over the greater occipital nerve of the C2 root; ipsilateral shoulder/arm pain; unilaterality without side-shift. Similar findings are usually not made in common migraine. Typical migraine symptoms, such as nausea, vomiting, photophobia, and phonophobia also occur in cervicogenic headache, but less frequently and to a lesser degree. Operative procedures directed to occipital/nuchal structures may afford decisive differentiation between the two disorders. In our estimation, cervicogenic headache and common migraine are two distinct disorders, with their own clinical patterns, pathogenesis, treatment - and, in all probability, also prognosis.

Common migraine ("migraine without aura"): localization of the initial pain of attack.

In classical migraine ("migraine with aura"), the attack pain is usually initially felt in the oculo-fronto-temporal area (around 90% of the cases). A fronto-temporal onset of pain is in other words a typical trait of classic migraine. The initial location of pain in common migraine ("migraine without aura") is not so well known. In the present study, 32 migraine patients and 29 cervicogenic headache patients were compared as for localization of pain onset. Twenty-four of 32 migraine patients (75%) felt the initial pain in the oculo-fronto-temporal area; in 28 of 32 cases the onset was in the "anterior" parts (88%). The corresponding figures in the cervicogenic group were: 5 of 29 (17%) and 6 of 29 (21%) respectively. There is thus a clear-cut difference between the two groups in this respect. The initial localization of pain can probably also be used for diagnostic purposes. The similarity between classic and common migraine in this respect is striking.

Laterality of pain and other migraine criteria in common migraine. A comparison with cervicogenic headache.

Patients diagnosed as suffering from common migraine according to the "Ad hoc committee" criteria of 1962 have been studied as for type of unilaterality of headache. Patients, with trauma to the face, head, and neck were excluded, together with patients with the faintest suspicion of aura and those with chronification of the headache. Common migraine criteria, as stipulated by the IHS and Vahlquist, were counted in every patient (n = 32), except the laterality which was a free variable (a total of 8 variables remaining). For comparison, as far as the number of migraine criteria is concerned, a group of cervicogenic headache patients was also studied (n = 30). Unilaterality with side shift of pain was present in 75% in the common migraine group; in 34% of the patients, a combined pattern, i.e. bilateral headache + unilaterality with sideshift was present. Common migraine, therefore, just as classic migraine, seems to be a headache characterized by unilaterality with side alternation of pain. Common migraine criteria were present to a high degree in common migraine patients selected in this way, i.e. ca. 6.8 of a maximum of 7. In cervicogenic headache, the corresponding figure was ca. 3.8 (of a maximum of 7). These figures are statistically significantly different (p < 1.3 10(-11), Mann-Whitney test). Still, the level of criteria is relatively high in cervicogenic headache, and 6 of 30 patients would fulfil the IHS common migraine criteria.

Pain threshold in humans. A study with the pressure algometer.

Pain perception threshold (PPT) in the head was assessed with a pressure algometer in 40 control individuals (24 females and 16 males). Threshold was assessed at 11 symmetrical points on each side. The average threshold for each side was calculated, and differences between two sides were evaluated with an asymmetry index. Subjects were studied in relation to age and sex, and any difference in the symmetrical perception of pain on the head was registered. The deltoid muscle was chosen as a reference point, since it is rarely a site of trigger points. The reproducibility of the method was satisfactory. A significantly positive correlation was found between PPT value of the head and the deltoid muscle. There was no tendency to rise or fall in PPT during the same "session", which consisted of 3 separate complete measurements. The mean of mean values showed that there was little asymmetry as for the thresholds pertaining to the head in the total material. Age and sex apparently played little role as for the outcome of the test. The assessment of PPT in the head might be a useful tool in the study of lateralization of pain in unilateral headache syndromes.

[Cervicogenic headache: report of a case]. / Cefaléia cervicogênica: relato de um caso.

It has been known for many years that headaches can originate from abnormalities in the neck. However, their clinical pictures were never sufficiently systematized, at least not in order to permit the research on their pathogenesis. Sjaastad et al. described in 1983 a group of patients with a very uniform and stereotyped headache. Attacks of mild, longlasting, unilateral head pain without sideshift, occurred every few weeks. The headache could be provoked by neck movements, such as extension, rotation or lateral flexion, as well as by external pressure towards trigger points in the neck. It usually started back in the neck, eventually spreading to the ipsilateral orbito-frontal-temporal or facial areas. The denomination "cervicogenic headache" (CH) was proposed. Its pathophysiology is presently unknown. The C2 and occipital nerve blockages eliminate the pain. We present a CH case and make some comments on its clinical picture, pathophysiology, and treatment.

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.

Sick leave is related to frequencies of migraine and non-migrainous headache--The HUNT Study.

The aim of this large, cross-sectional, population-based study was to examine the association between sick leave and headache. Between 1995 and 1997, all 92 566 adults in Nord-Trøndelag County in Norway were invited to participate in a health survey. Out of 73 327 invited individuals <67 years old, a total of 38 192 (52%) responded to questions about headache, work situation and sick leave during the past year. Associations between sick leave, headache and migraine included were assessed in multivariate analyses, estimating prevalence odds ratios (ORs) with 95% confidence intervals (CIs). There was an increasing prevalence of sick leave with increasing frequency of migraine and non-migrainous headache. The prevalence of sick leave >8 weeks during the past year was more than three times higher among individuals with headache >14 days per month (20%) compared with those without headache (6%). The results may indicate that better treatment of individuals with chronic headache may have beneficial economic implications.

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.