Carla Zanferrari

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.

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.

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.

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.

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.

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.

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 (κ = 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.

α‐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 α‐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 α‐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 patients 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 α‐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 α‐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 α‐dihydroergocryptine and flunarizine, respectively. Based on the overall improvement in migraine parameters, α‐dihydroergocryptine can be recommended for use in migraine prophylaxis.

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) T2-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 Scheltens 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.