Neuropeptide Y in Juvenile Migraine and Tension-Type Headache

SYNOPSIS
Neuropeptide Y (NPY) is widely distributed throughout sympathetic nerve endings where it is co-stored and co-secreted with noradrenaline. It is considered a marker of noradrenergic function. To determine the role of NPY in the pathogenesis of juvenile headache, we determined its plasma levels in two groups of young migraine patients (with and without aura), in a group of episodic tension-type headache patients and in a group of age and sex-matched healthy subjects. Significantly lower plasma levels of NPY were evident in the migraine patients with aura (P<0.001) and, to lesser extent, in the migraine patients without aura (P<0.02), both assessed in the interictal period, with respect to the control group. Plasma NPY levels tended to significantly increase during attacks in migraine patients with aura (P<0.0009). A less evident, though significant increase was also present during attacks in migraine patients without aura (P<0.02). No significant variations were observed between headache-free periods and attacks in tension-type headache patients. Reduced NPY levels in the interictal period can be considered further evidence of the derangement of the sympathetic function in the course of migraine, particularly that with aura. The increase in NPY levels during migraine attacks could be an expression of sympathetic activation, even though the functional status of this system is less efficient.     

Intravenous dipyrone in the acute treatment of migraine without aura and migraine with aura: a randomized,double blind,placebo controlled study

BACKGROUND: Dipyrone (Metamizol) has been used in the acute treatment of migraines in Brazil. Some investigators have found it to be a highly effective medication for migraine pain and associated symptoms. OBJECTIVE: To conduct a randomized, placebo controlled, double blind study to assess the effect of dipyrone on the pain and symptoms associated with migraine without aura or with aura and the adverse effect profile of this medication. METHODS: For the migraine without aura group, 44 patients were assigned at random to receive 1 g intravenous dipyrone, and 30 patients received 10 mL 0.9% physiological saline. For the migraine with aura group, 30 patients received both dipyrone or placebo. We used seven parameters of analgesic evaluation and an analog scale to assess nausea, photophobia, and phonophobia. RESULTS: Patients receiving dipyrone demonstrated a statistically superior improvement (P<.05 and P<.01) in pain and all associated symptoms compared with control subjects. CONCLUSIONS: Dipyrone is an effective drug for the relief of acute migraine pain and associated symptoms.     

Weekend headache: a retrospective study in migraine without aura and episodic tension-type headache

Our retrospective study was aimed at determining the existence of weekend headache and, if so, whether it has the same clinical features as migraine without aura and episodic tension-type headache, or whether it occurs as a separate form of headache which could find its own place in the International Headache Society classification.
For this study, we reviewed the clinical records of 120 patients with migraine without aura and 120 patients with episodic tension-type headache randomly selected among all those referred to the Headache Center of the University of Parma Institute of Neurology between 1985 and 1996.
A review of these records suggests that weekend headache exists for both types of headache considered. Clinically, it is interesting to note that the male-to-female ratio for the weekend form of tension-type headache was 1:1, as opposed to 1:3 for general episodic tension-type headache. As regards classification, no evidence so far seems to suggest that weekend headache should be considered as an independent entity. Apart from certain features that appear to be peculiar to this form of headache—such as increased pain intensity—it thoroughly fulfills the diagnostic criteria of the primary headaches from which it evolves. Finally, a few clinical features suggest that the weekend may simply be a triggering factor in migraine without aura attacks, while playing a major role in episodic tension-type headache. However, weekend headache is a clinical entity that clearly needs further study.     

Platelet superoxide dismutase in migraine and tension-type headache

Superoxide dismutase (SOD) is a radical-scavenging enzyme. We determined Cu, Zn-SOD concentrations and activities in platelets from subjects with migraine and tension-type headaches. Thirty migraine without aura (MWoA) patients, 9 migraine with aura (MWA) patients, and 53 tension-type headache patients were selected for study. Thirty healthy volunteers composed the control group. Concentrations of platelet SOD were determined using enzyme-linked immunosorbent assay techniques. The activity of platelet SOD was determined by measuring reductivity of nitroblue tetrazolium. Low concentrations of platelet SOD were found in patients with MWA and MWoA. Platelet SOD activity decreased in MWA patients but not in patients with MWoA or tension-type headaches. These findings suggest vulnerability to oxidative stress in patients with migraine. It is suggested that low platelet SOD levels may play an important role in the etiology of migraine.     

Migraine with aura versus migraine without aura: pain intensity and associated symptom intensities after placebo

OBJECTIVE: To compare the intensity of pain and associated symptoms after placebo administration in patients with migraine with aura and migraine without aura. BACKGROUND: Studies that evaluate drugs used in the acute treatment of migraine ideally should include a placebo arm. The International Headache Society also recommends stratification according to age and sex but not by the presence versus absence of aura. METHODS: The study was conducted as part of a placebo controlled randomized survey comparing four active drugs against placebo in the acute treatment of migraine. Patients were blinded as to treatment received. Placebo consisted of 10 mL of normal saline (0.9%) intravenously. Pain intensity was evaluated by a 10-point analogical-verbal scale. Nausea, photophobia, and phonophobia were evaluated by a four-point analogical-verbal scale. For statistical analysis, unpaired t-test with Welch correction was used. RESULTS: After placebo administration, reduction of symptom intensity (pain, nausea, photophobia, and phonophobia) in patients with migraine without aura was significantly greater than that observed in patients with migraine with aura. CONCLUSIONS: Our findings suggest that studies comparing placebo against an active drug should use stratification according to the presence versus absence of aura.     

Improved description of the migraine aura by a diagnostic aura diary

We present a diagnostic aura diary for prospective recordings of migraine with aura. Three questionnaires are supplemented with sheets for drawings and plottings of visual and sensory auras. Twenty patients recorded 54 attacks of migraine with aura and 2 attacks of migraine aura without headache. The visual and sensory aura were usually gradually progressive, reaching maximum development in 15 and 25 min (median) respectively and had a total duration of 20 and 55 min (median) respectively. Approximately 13% of the attacks had acute onset of visual aura associated with other features more typical of migraine. The visual and sensory auras always preceded typical migraine headache, and headache occurring before aura symptoms was always of the tension type, The migraine headache was milder than in attacks of migraine without aura and often did not have migraine characteristics. In attacks with unilateral head pain, headache and aura symptoms were contralateral in 90% and ipsilateral in 10%.     

Quantitative EEG in Children with Headache

SYNOPSIS
The object of this work is to determine if Brain Mapping can reveal significant differences between a normal control group and e group whose members suffer from one of three types of headache: tension-type, migraine with aura and migraine without aura. Both groups were formed by children aged between 6 and 14; the latter were undergoing no treatment and were in a headache-free phase.
Results demonstrate that there are no significant differences between the control group and the tension-type headache group. Neither were differences found in migraine without aura group but in migraine with aura there was an increase of the theta/alpha ratio in the temporal posterior and occipital zones. This ratio could be used as a neurophysiological indicator in the evolution of the migraine with aura pathology.     

Posterior cerebral hypoperfusion in migraine without aura

In cerebral blood flow studies, migraine aura is characterized by a posterior cortical hypoperfusion. In contrast, only rare and mild changes in brain perfusion have been demonstrated in migraine without aura, suggesting two different haemodynamic patterns in migraine with and without aura. Our aim was to study hypoperfusion with positron emission tomography (PET) as early as possible during spontaneous migraine without aura attacks. We used H₂¹⁵O PET to investigate seven patients (six female, one male) with migraine without aura (International Classification of Headache Diseases-II code 1.1) in three situations: during the headache phase, after headache relief following sumatriptan injection, and during an attack-free interval. Statistical analysis was performed with SPM2. Within 4 h after the attack onset, significant relative bilateral posterior cortical hypoperfusion was found and persisted after headache relief following sumatriptan injection. A posterior cortical hypoperfusion demonstrated in migraine without aura could suggest a common pathogenesis in migraine with and without aura. The significance of relative posterior hypoperfusion in migraine without aura is discussed according to the current knowledge of migraine pathogenesis.     

Acute and interictal allodynia in patients with different headache forms: an Italian pilot study

OBJECTIVE: To investigate allodynia in patients with different primary headaches. BACKGROUND: Many migraineurs have allodynia during headache attacks; some may have allodynia outside attacks; allodynia may also be associated with other primary headaches. METHODS: A total of 260 consecutive primary headache patients presenting for the first time at a headache center, and 23 nonheadache controls answered written questions (subsequently repeated verbally) to determine the presence of acute and interictal allodynia. RESULTS: We divided the patients into: episodic migraine (N = 177), subdivided into only migraine without aura (N = 114) and those sometimes or always reporting migraine with aura (N = 63); episodic tension-type headache (N = 28); chronic headaches (headache > or = 15 days/month, N = 52), including chronic migraine, chronic tension-type headache, and medication-overuse headache; and other headache forms (N = 3). Acute allodynia was present in 132 (50.7%), significantly more often in patients sometimes or always suffering migraine with aura, and those with chronic headache forms, compared to patients with migraine without aura and episodic tension-type headache. Interictal allodynia was present in 63 (24.2%) patients, with significantly higher frequency in those having migraine with aura attacks than controls and common migraine patients. CONCLUSIONS: Allodynia is not specific to migraine but is frequent in all headache patients: acute allodynia was reported in half those interviewed and in over a third of patients in each headache category; interictal allodynia was reported by nearly 25%.     

Serum levels of N-acetyl-aspartate in migraine and tension-type headache

Serum levels of N-acetyl-aspartate (NAA) may be considered a useful marker of neuronal functioning. We aimed to measure serum NAA in cohorts of migraine and tension-type headache patients versus controls, performing correlations with main clinical features. A total of 147 migraine patients (including migraine without aura, with aura and chronic migraine), 65 tension-type headache (including chronic and frequent episodic tension-type headache) and 34 sex- and age-matched controls were selected. Serum was stored at −80 °C. Quantification of NAA was achieved by the standard addition approach and analysis was performed with liquid-chromatography–mass-spectrometry (LC/MS) technique. The NAA levels were significantly decreased in migraine group (0.065 ± 0.019 mol/L), compared with both tension-type headache patients (0.078 ± 0.016 mol/L) and controls (0.085 ± 0.013 mol/L). Control subjects were significantly different from migraine with and without aura and chronic migraine, who differed significantly from episodic and chronic tension-type headache. Migraine with aura patients showed lower NAA levels when compared to all the other headache subtypes, including migraine without aura and chronic migraine. In the migraine group, no significant correlation was found between NAA serum levels, and headache frequency, allodynia and interval from the last and the next attack. The low NAA in the serum may be a sign of neuronal dysfunction predisposing to migraine, probably based on reduced mitochondria function.     

Intravenous chlorpromazine in the emergency department treatment of migraines: a randomized controlled trial

The aim of this study is to assess, in a double blind randomized clinical trial, the effect of chlorpromazine (CPZ) on the pain and associated symptoms in patients with migraine. Sixty patients with migraine with aura and 68 patients with migraine without aura were assigned at random to receive IV 0.1 mg/Kg CPZ or placebo. We assessed pain intensity, nausea, photophobia, and phonophobia at baseline, 30 min, and 60 min post-IV administration. End-point efficacy at 60 min was used to calculate the number needed to treat (NNT). We also recorded adverse effects, need for rescue medication at 24 h, and recurrence of headache at 24 h. We found clinically and statistically significant (p < 0.01) improvement associated with CPZ in pain scores, nausea, photophobia, phonophobia, and need for rescue medication, all at 60 min, and in rate of recurrence at 24 h, both in patients with and without aura. NNT = 2. Those allocated to CPZ had less nausea and dyspepsia, but more drowsiness and postural hypotension than those receiving placebo. CPZ is an excellent option for the treatment of migraines, with and without aura, in the Emergency Department.     

灵通胶囊治疗头痛的临床研究

目的:观察灵通胶囊对无先兆偏头痛(Migraine without aura)和高频发作性紧张型头痛(Fre-quent episodic tension-type headache,FETTH)的即时止痛疗效。方法:头痛患者共95例随机分配到灵通组和元胡组(对照组)。其中无先兆偏头痛入灵通组25例服药51例次,入元胡组28例服药53例次;FETTH入灵通组25例服药39例次,入元胡组17例服药27例次。分别于疼痛时即时服用灵通胶囊2粒和元胡止痛颗粒2包。将疼痛程度分级量化,由患者记录服药前和服药后2小时内每30分钟时的疼痛程度。以服药后2小时疼痛减轻程度≥50%作为有效。结果:无先兆偏头痛有效率在灵通组为68.6%,在元胡组为32.1%(P<0.001);FETTH有效率在灵通组为76.9%,在元胡组为59.3%(P>0.05);两种头痛的综合有效率在灵通组为72.2%,在元胡组为41.3%(P<0.001)。灵通组在服药30分钟后各时点的疼痛评分显著低于元胡组(P<0.001)。结论:灵通胶囊对两种头痛有明显的即时止痛疗效。     

Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura. A randomized,double-blind,placebo-controlled study

Magnesium sulphate has been used in the acute treatment of migraines; some studies found it to be a highly effective medication in the acute control of migraine pain and associated symptoms. This randomized, double-blind, placebo-controlled study assesses the effect of magnesium sulphate on the pain and associated symptoms in patients with migraine without aura and migraine with aura. Sixty patients in each group were assigned at random to receive magnesium sulphate, 1000 mg intravenously, or 0.9% physiological saline, 10 ml. We used seven parameters of analgesic evaluation and an analogue scale to assess nausea, photophobia and phonophobia. In the migraine without aura group there was no statistically significant difference in the patients who received magnesium sulphate vs. placebo in pain relief. The analgesic therapeutic gain was 17% and number needed to treat was 5.98 at 1 h. There was also no statistical difference in relief of nausea. We did observe a significant lower intensity of photophobia and phonophobia in patients who received magnesium sulphate. In the migraine with aura group patients receiving magnesium sulphate presented a statistically significant improvement of pain and of all associated symptoms compared with controls. The analgesic therapeutic gain was 36.7% at 1 h. A smaller number of patients continued to have aura in the magnesium sulphate group compared with placebo 1 h after the administration of medication. Our data support the idea that magnesium sulphate can be used for the treatment of all symptoms in migraine with aura, or as an adjuvant therapy for associated symptoms in patients with migraine without aura.     

Quality of life of patients with cervicogenic headache: a comparison with control subjects and patients with migraine or tension-type headache

OBJECTIVE: To establish the health-related quality of life of patients with cervicogenic headache and to compare it with a random Dutch sample of control subjects and with patients with migraine without aura or with episodic tension-type headache. METHODS: Thirty-seven patients with cervicogenic headache, 42 patients with episodic tension-type headache, and 39 patients with migraine without aura completed a Medical Outcomes Study 36-Item Short Form questionnaire. RESULTS: Domain scores for "physical functioning" of patients with cervicogenic headache were worse than those of patients with migraine or tension-type headache. Physical functioning scores were lower for patients with tension-type headache than for those with migraine. Migraineurs reported a diminished score for "social functioning" compared to patients with tension-type headache. All Medical Outcomes Study 36-Item Short Form domain scores were significantly lower for patients with cervicogenic headache relative to the control group. CONCLUSIONS: Patients with cervicogenic headache have a quality of life burden that is substantial. Although impairment in the quality of life of patients with cervicogenic headache is comparable to patients with migraine without aura and those with episodic tension-type headache, there are some specific differences.     

Beta-endorphin concentrations in the peripheral blood mononuclear cells of migraine and tension-type headache patients

Levels of beta-endorphin in peripheral blood mononuclear cells have been studied as a new approach to investigating opioid tone in migraine and tension-type headache. Sixty-one patients with migraine without aura, 39 with migraine with aura and 23 with episodic tension-type headache were compared with 37 healthy controls. Peripheral blood samples were taken from patients not enduring headache attacks and not undergoing prophylactic treatment. A significant reduction in peripheral blood mononuclear cell beta-endorphin concentrations was observed in migraine patients with and without aura, but not in tension-type headache patients. Altered transmitter modulation to peripheral blood mononuclear cells may be the cause of this alteration, which could be part of a more diffuse opioid system derangement in migraine subjects.     

Providing relief from headache pain. Current options for acute and prophylactic therapy

The sometimes debilitating pain of migraine and other types of primary headache can be difficult to control with acute drug therapy alone. Often patients need both acute and prophylactic treatment to keep headache pain at bay. Dr Ward discusses the current treatment options for migraine with and without aura, tension-type headache, and cluster headache. He also provides practical pointers for use of the various formulations of specific drugs, including the newer "triptan" medications.     

A prospective study of migraine with aura attacks in a headache clinic population

In order to investigate the prevalence of migraine with aura (MA) attacks according to the criteria set by the International Headache Society (IHS) for diagnosis down to the three-digit level of classification, and to determine the recurrence and possible variability of MA attacks over time, we conducted a 6-15-month-long prospective study on 64 MA patients (42 women and 22 men) consecutively referred for the first time to the University of Parma Headache Centre. At the end of the follow-up period, diagnosis was the same as at the first visit for 80.0% of patients, while it was changed for 20.0%. Throughout the duration of the study, the average number of attacks for each patient was 5.3 +/- 6.2 (range 0-30). Attacks of migraine with typical aura were the most frequent (69.1% of patients), but migraine aura without headache (29.1%) and migraine with prolonged aura (20.0%) were also common; by contrast, basilar migraine and migraine with acute onset aura were reported only by one patient in either case. Migraine aura without headache was statistically significantly more frequent in males than in females. Our study results suggest that in most cases the frequency of recurrent MA attacks is relatively low and provide interesting indications about the prevalence of the different MA subtypes listed in the IHS classification, albeit in a headache clinic population.     

Outcome of juvenile headache in outpatients attending 23 Italian headache clinics. Italian Collaborative Study Group on Juvenile Headache (Società Italiana Neuropsichiatria Infantile [SINPI])

A multicenter 3-year follow-up study was carried out on young patients with headache referred to tertiary headache centers or pediatric clinics. Three years after the first examination in 1993, 442 (of an original sample of 719) young outpatients with headache (226 females and 216 males) were re-examined. The diagnostic criteria of the International Headache Society (IHS) and those modified for migraine without aura by Winner et al were applied at both the baseline evaluation and the 3-year re-examination. At the follow-up, 290 children still had headache, 101 were in clinical remission, and 51 had dropped out. Using the current diagnostic criteria, only 46.2% of patients having migraine without aura, 50% of those having migraine with aura, and 35.3% of those suffering from migraine disorders which do not fulfill IHS criteria for migraine received the same diagnosis at the time of follow-up. The percentage of patients receiving a diagnosis of migraine without aura rose significantly when new modified criteria were used (60.5%), whereas a drop in the frequency of migraine disorders not fulfilling IHS criteria was observed at follow-up, both in patients with the diagnosis of migraine without aura at the first examination (4.6%) and in patients with migraine not always fulfilling IHS criteria at the first examination (6.2%). Among all patients who received this latter diagnosis at the first examination, it was possible to make a diagnosis of migraine with aura at the follow-up in 8.8% of cases and that of migraine without aura in 26.5%. No significant variations in the frequency of either episodic tension-type headache or chronic tension-type headache were found, with the exception of a slight decrease in the percentage of tension-type headache which did not fulfill IHS criteria, but the difference between the first examination and the follow-up values does not reach the level of statistical significance (5% versus 12%). As far as the evolution of migraine is concerned, 17.4% of patients with migraine were headache-free at the 3-year follow-up. In tension-type headache, the percentage of patients who were headache-free was particularly high in those with the episodic form (32.9%) and in those suffering from tension-type headache not fulfilling IHS criteria (29.1%). The majority of patients who had been diagnosed as having unclassifiable headache at the first examination received a correct diagnosis at the follow-up with the exception of one patient. As observed in adult patients, variations in the headache characteristics were also observed in children and adolescents (that is, migraine with aura can change to migraine without aura, or the latter can transform into episodic tension-type headache or chronic tension-type headache can change into the episodic form). This follow-up study was aimed at reaching a better understanding of headache disturbances in children and adolescents, examining, in particular, variations of headache with time in this stage of life.     

Magnetic Resonance Imaging in Migraine and Tension-Type Headache

Cerebral magnetic resonance imaging was performed on 63 patients with chronic primary headache (28 with migraine with and without aura, 35 with tension-type headache). Fifty-four headache-free individuals of the same age range were used as controls. The headache sufferers showed an incidence of focal white matter abnormalities on T2-weighted magnetic resonance imaging significantly higher than the age-matched control group (33.3% vs 7.4%). The incidence of white matter abnormalities did not correlate with age (except for patients older than 60 years), sex, headache history, headache status, or ergotamine consumption. Migraine (with and without aura) and tension-type headache patients had similar prevalence of white matter abnormalities (32.1% vs 34.3%). The lesions were predominantly distributed in the frontal region, independent of the side of usual aura or headache. Our findings indicate that both migraine and tension-type headache may be associated with early pathologic changes in the brain and may share, at least in part, common pathogenic pathways.