Cerebral distribution of white matter lesions in migraine with aura patients.

OBJECTIVE: The objective of the study was to compare the cerebral distribution of white matter lesions (WMLs) between migraine patients with different aura symptoms. METHODS: Migraine with aura (MA) patients were consecutively enrolled as part of the Shunt-Associated Migraine (SAM) study. According to clinical symptoms, aura was classified as motor, aphasic, sensory, visual or vertebrobasilar. Standard and FLAIR (fluid attenuated inversion recovery) T(2)-weighted MRI sequences were inspected for WMLs by three independent raters blinded to clinical data. WMLs were assessed in the periventricular areas (PV-WMLs) with the Fazekas scale and in the deep white matter (D-WMLs) with the Schelten's scale. Interobserver agreement was good to excellent (k = 0.64 to 0.96, p < .0001). RESULTS: One hundred and eighty-five patients (77% women) were included. Aura symptoms were classified as visual in 172 (99%) patients, sensory in 76 (42%), aphasic in 54 (30%), motor in 39 (21%) and vertebrobasilar in 17 (9%) patients. One hundred and four patients (57%) exhibited more than one type of aura. D-WMLs were mainly detected in the frontal lobes (86%). There was no association between type of aura and the presence of WMLs in any cerebral location. CONCLUSION: Aura symptoms do not influence the cerebral distribution of WMLs associated with migraine disease.

Right-to-left shunt does not increase white matter lesion load in migraine with aura patients.

BACKGROUND: White matter lesions (WMLs) are commonly found on brain MRI of migraine patients. Migraine with aura (MA+) is associated with an increased frequency of right-to-left shunt (RLS) mostly due to patent foramen ovale. The relationship between WML load and RLS in MA+ is currently unknown. METHODS: MA+ patients were consecutively enrolled as part of the Shunt Associated Migraine (SAM) study. Patients underwent a standardized headache and vascular risk factors questionnaire, contrast-enhanced transcranial Doppler, blood coagulation tests, and brain MRI. RLS was categorized into four grades: no shunt, <10 microbubbles (mb), >10 mb single spikes pattern, and >10 mb shower/curtain pattern. Standard and fluid-attenuated inversion recovery T2-weighted MRI sequences were inspected for WMLs by three independent raters blinded to RLS grade. WML load was scored in the periventricular areas (PV-WMLs) with the Fazekas scale and in the deep white matter (D-WMLs) with the Scheltens scale. Interobserver agreement was good to excellent (kappa = 0.64 to 0.96, p < 0.0001). WML load was then correlated between patients with and without RLS. RESULTS: One hundred eighty-five patients (77% women) were included. PV-WML load was similar between patients with and without RLS. D-WML load decreased in patients with RLS (p = 0.045). On logistic regression analysis, only age was associated with WMLs (p < 0.001). CONCLUSIONS: The presence of right-to-left shunt does not increase white matter lesion load in patients who have migraine with aura.

Is migraine associated with right-to-left shunt a separate disease? Results of the SAM study.

Migraine with aura (MA) is associated with the persistence of patent foramen ovale (PFO) in about 50% of cases, and migraineurs tend to have larger shunts than controls, suggesting that right-to-left shunt (RILES) determined by PFO could play a role in triggering migraine attacks. Moreover, some preliminary reports have suggested that PFO closure may give relief to both migraine and aura attacks. The aim of this study was to clarify if shunt-associated migraine (SAM) has clinical features that allow a distinction from shunt-unrelated migraine (SUM), in a prospective, multicentre, observational study (SAM study). We enrolled consecutive MA patients, who underwent a structured, standardized questionnaire for family and personal history and for detailed migraine features. All were systematically screened for RILES with transcranial Doppler, and for coagulation disorders. Overall, 460 patients were included; the SUM and SAM classes comprised 58% and 42% of patients, respectively. SAM patients were significantly younger (34.1 +/- 10 vs. 37.1 +/- 11 years), had a more frequent family history of migraine (76% vs. 66%) and a higher frequency of sensory symptoms of aura (51% vs. 41%); by contrast, there was a lesser association of SAM with other cardiac abnormalities and with coagulation disorders. The SAM study suggests that the effect of RILES on migraine features is not relevant. The higher family history of migraine in SAM suggests a possible genetic linkage between migraine and RILES.

Arterial hypertension as risk factor for spontaneous cervical artery dissection. A case-control study.

Because of the presumed non-atherosclerotic pathogenesis, the potential link between spontaneous cervical artery dissection (sCAD) and common risk factors for atherosclerosis has never been investigated systematically. Therefore, this prospective, multicentre, case-control study compared the frequency of tobacco use, hypertension, diabetes mellitus, and hypercholesterolaemia among a group of consecutive patients with sCAD (n = 153), a group of patients with ischaemic stroke, not related to CAD (non-CAD), and a group of controls. As opposed to the other variables, a trend towards a significant association was seen when the prevalence of hypertension was compared among patients with sCAD and controls (26.8% v 17.0%; odds ratio (OR) 1.79; 95% confidence interval (CI), 0.98 to 3.27; p = 0.058). Hypertension was also significantly associated with the subgroup of patients with sCAD and cerebral infarction (OR, 1.94; 95% CI, 1.01 to 3.70; p = 0.045), particularly when involving the vertebral arteries (OR, 2.69; 95% CI, 1.20 to 6.04; p = 0.017). These findings might help define the spectrum of pathogenic conditions predisposing to sCAD and provide information to help investigate the combined effect of such susceptibility factors in future studies.

History of migraine and the risk of spontaneous cervical artery dissection.

The pathophysiology of spontaneous cervical artery dissection (sCAD) is largely unknown. An association with migraine has been suggested, but not definitively proven. In the setting of a hospital-based prospective case-control study we assessed personal and family history of migraine in 72 patients with sCAD, 72 patients with cerebral infarct unrelated to a CAD (non-CAD) and 72 control subjects. Personal history of migraine was significantly associated to sCAD compared to non-CAD (59.7% vs. 30.6%; OR 3.14; 95% CI 1.41-7.01) and controls (18.1%; OR 7.41; 95% CI 3.11-17.64). As opposed to migraine with aura, migraine without aura was significantly more frequent among sCAD than among non-CAD (56.9% vs. 25.0%; OR 3.91; 95% CI 1.71-8.90) and controls (12.5%; OR 9.84; 95% CI 3.85-25.16). Similar results were observed when the frequencies of family history of migraine were compared. These findings are consistent with the hypothesis that migraine may represent a predisposing condition for sCAD.

Effect of adenosine on cerebral blood flow velocity.

BACKGROUND AND PURPOSE: Evidence suggests that adenosine (ADN) is a potent vasodilator of cerebral vessels. However, the feasibility of manipulating human cerebral vascular resistance with ADN has not been assessed by means of TCD. The purpose of this study was to quantitatively estimate the change in middle cerebral artery cerebral blood flow velocity (CBFV) in response to intravenous ADN infusion in humans. METHODS: Eleven patients with subacute cerebrovascular events (ischemic stroke, transient ischemic attack, or hemorrhage) undergoing adenosine-thallium stress testing were studied before, during, and after ADN infusion to evaluate the effect of ADN on cerebral blood flow velocity. Continuous blood pressure (BP), heart rate (HR), respiration rate (RR), end-tidal CO2 (ET-CO2), and transcranial Doppler ultrasonography monitoring of CBFV and pulsatility index (PI) in both middle cerebral arteries were performed. RESULTS: The mean CBFVs were 65.4 +/- 19.2 cm/s before, 55.4 +/- 18.1 cm/s during, and 64.1 +/- 22.5 cm/s after ADN infusion, which represents a statistically significant decrease during ADN test compared with both baseline (P = .007) and posttest levels (P = .017). The PI was increased during the test (0.91 +/- 0.2) when compared with baseline (0.71 +/- 0.1) (P = .007). During ADN injection, mean HR increased (P = .004) and mean ET-CO2 levels decreased significantly (P = .003). Mean BP and RR did not change significantly. CONCLUSIONS: The authors hypothesize that any direct vasodilatory effect of ADN on the distal cerebral peripheral vasculature may be negated by an effect of ADN on depth of respiration resulting in hypocapnia and secondary distal vasoconstriction.

Alpha-dihydroergocryptine in the prophylaxis of migraine: a multicenter double-blind study versus flunarizine.

This multicenter, double-blind, clinical study was designed to compare the efficacy and safety of alpha-dihydroergocryptine and flunarizine in the prophylaxis of migraine without aura. One hundred thirty-five patients fulfilling the diagnostic criteria of the International Headache Society were enrolled at five neurologic centers. The study design included a 1-month pretreatment phase with placebo; a 6-month, double-blind, double-dummy treatment phase with alpha-dihydroergocryptine (10 mg twice daily) or flunarizine (5 mg once daily); a further 3-month follow-up phase without treatment. Efficacy was assessed using the patient's diary. Laboratory tests, vital signs, and adverse events were monitored. Analysis of covariance for repeated measures was performed on the intent-to-treat sample. Both treatments led to a significant reduction in the frequency of migraine, days with headache, and use of relief medication. Overall, 51% of those treated with alpha-dihydroergocryptine and 49% of those treated with flunarizine were responders (50% or greater reduction in attack frequency), the average percentage of reduction being 64% with alpha-dihydroergocryptine and 51% with flunarizine. There was no significant difference between the two groups in terms of incidence of adverse events; dizziness and weight gain were the most frequent observed adverse events with alpha-dihydroergocryptine and flunarizine, respectively. Based on the overall improvement in migraine parameters, alpha-dihydroergocryptine can be recommended for use in migraine prophylaxis.

Classification of chronic daily headache by International Headache Society criteria: limits and new proposals.

We conducted a retrospective study of 150 patients with chronic daily headache (CDH) to determine how to categorize their headache according to the classification of the International Headache Society (IHS). All patients were first evaluated at Parma and Pavia Headache Centres (from January 1992 to March 1993) and had had headache for at least 15 days a month during the previous 6 months. Four patients were thereafter excluded due to poor reliability. The 146 patients who met our CDH criteria (92 with and 54 without clear-cut migraine attacks) could be classified into four groups: (i) chronic tension-type headache (CTTH)--27 patients; (ii) coexisting migraine plus CTTH--65 patients; (iii) unclassifiable daily headache--27 patients; and (iv) migraine and an unclassifiable interval headache--27 patients. Seventy-two percent of patients with CDH had migraine as the initial form of their headache. We therefore propose to revise the IHS classification for migraine, taking into account its evolution, and add two subcategories, migraine with interparoxysmal headache and chronic migraine.

International Headache Society classification: interobserver reliability in the diagnosis of primary headaches.

We assessed interobserver reliability of the International Headache Society (IHS) classification for diagnosis of primary headaches. The study was performed on 103 patients consecutively seen at two Headache Centres. Each patient was given a structured interview recorded on videotape. Four experienced clinicians then reviewed the interviews separately and made a diagnosis of headache according to IHS criteria at the one- and two-digit levels. At both the one- and the two-digit level the agreement was substantial (Kappa = 0.74 and 0.65, respectively). The analysis of reliability for each of nine items necessary for diagnosis showed an agreement ranging from substantial (Kappa = 0.69) to almost perfect (Kappa = 0.89). Our results indicate that the IHS classification has a good reliability for the diagnosis of primary headaches at the one- and two-digit levels.

Migraine without aura and reproductive life events: a clinical epidemiological study in 1300 women.

A retrospective study was conducted on 1300 women suffering from migraine without aura referred to the Headache Centers of Parma and Pavia from 1984 to 1990. All the data concerning their reproductive life, and the modifications induced by it on the course of headache were obtained from record-charts. Migraine frequently started at menarche (10.7%); in 60% of cases the migraine attacks occurred mostly or exclusively in the perimenstrual period, in 67% of cases disappeared during pregnancy, and in 24.1% significantly (P < 0.0001) worsened with "pill" intake. This study also designated a migraine subgroup which is more influenced by changes in sexual hormones, i.e. migraine with onset at menarche. This form of migraine shows more frequently a menstrual periodicity, and usually improves during pregnancy. Furthermore, menstrual migraine patients show social and cultural characteristics with distinguish them from other women.

A computerized record chart for the study of chronic daily headache.

A comprehensive record chart for the study of chronic daily headache (CDH) is presented. The record chart contains 11 parts (232 items) concerning: sociodemographic data, physiological history, female reproductive life history, family history, pathological history, drug abuse, headache history, headache clinical features, prophylactic therapy, instrumental investigations, and physical and neurological examination. Furthermore, three attached special charts are illustrated which concern, respectively, the cervical spine examination, oromandibular function examination and the assessment of analgesic use.

An epidemiological approach to the nosography of chronic daily headache.

Chronic daily headache (CDH), a heterogeneous group of headaches, includes different forms that occur daily, or almost daily, over a prolonged period of time. The nosography of this group is still a matter of debate, and in the most recent classification of the IHS (1988) only a few types of CDH are included: chronic tension-type headache, coexisting migraine. This study is an epidemiological approach to identifying the clinical features of CDH and the possible factors involved in changing episodic headache in CDH. Ninety CDH outpatients were investigated using a computerized record chart. The main observed forms were: (a) chronic tension-type headache--migraine with interparoxysmal headache, an evolved form of migraine in which a constant low severity headache develops between attacks; (b) transformed migraine, an evolved form of migraine with progressive worsening of the disease which reaches the level of continuous pain with the disappearance of typical migraine attacks. Interval headaches in migraine with interparoxysmal headache partly fulfil the IHS criteria for chronic tension-type headache. Analgesic drug abuse plays a prominent role in inducing CDH and in determining its clinical features.

Accompanying symptoms of cluster attacks: their relevance to the diagnostic criteria.

Two-hundred-and-fifty-one consecutive cluster headache (CH) patients referred to the Pavia and Parma Headache Centers were evaluated in order to verify the presence and recurrence of one or more autonomic symptoms. Data obtained show that in 2.8% of patients cluster attacks were not accompanied by localized autonomic symptoms, thus confirming the report of Ekbom. We observed a high prevalence of photophobia, nausea and vomiting. The IHS diagnostic criteria for CH may need to be modified. The high frequency of "general" autonomic symptoms seems to suggest a component of "central" drive in the physiopathology of cluster headache.

Cluster headache. Recent developments in clinical characterization and pathogenesis.

The preliminary results of some new studies on cluster headache (CH) point to: (a) the existence of a form, secondary episodic CH, which should be included in the classification of headache; (b) the significant role played by air temperature variations and the number of daylight hours on the onset of CH active periods. Data from the evaluation of pupil response to corneal stimuli suggest a widespread alteration of the pain/autonomic integrative processes at the level of the central nervous system. Finally, data on new preventive (i.e., verapamil and ozone) and symptomatic (i.e., hyperbaric oxygen and sumatriptan) treatments are reported.

Cluster headache--course over ten years in 189 patients.

One-hundred-and-eighty-nine cluster headache patients, referred to Parma and Pavia Headache Centres between 1976 and 1986 with a disease duration of over 10 years, were interviewed about the course of cluster headache. They were classified as episodic (n = 140) or chronic (n = 49) cluster headache patients on the basis of course during the year of onset. Episodic patients showed the following outcome: maintenance of an episodic form (primary episodic form) in 80.7% of cases, shift towards a chronic form (secondary chronic form) in 12.9% and shift towards an intermediate pattern ("combined" form) in 6.4%. In chronic patients, cluster headache was still chronic (primary chronic form) at the moment of observation in 52.4% of cases, while it turned into an episodic form ("secondary" episodic form) in 32.6% and into a "combined" form in 14.3%. Nineteen patients (10%) had had no attacks for at least three years at the moment of examination. We can conclude from our data that: cluster headache is a disease of long duration, perhaps lifelong; episodic cluster headache tends to worsen; chronic cluster headache may easily turn into a better prognostic episodic form; prophylactic drugs are unable to induce recovery. The following factors seem related to a poor outcome: a later onset, the male gender and a disease duration of over 20 years for the episodic forms.