Cinzia Aurilia

Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, Roma, Latium, Italy

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Publications (25)64.97 Total impact

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    ABSTRACT: Progesterone influences central neuronal excitability, a key event in migraine pathophysiology. Progesterone receptor gene (PGR) rs1042838 (G/T - Val660Leu) variant is indicative of PROGINS haplotype and associated to a reduced PGR activity. With the aim of investigating whether any type of association existed between this genetic variant and migraine pathophysiology, genotyping was performed in 380 consecutive migraine patients and 185 age-, sex-, and race-ethnicity-matched healthy controls from Interinstitutional Multidisciplinary BioBank (BioBIM) of IRCCS San Raffaele Pisana, Rome, Italy. rs1042838 genotypes did not correlate with demographics or clinical migraine features. However, TT (Leu) genotype was significantly associated with a later age of migraine onset: Patients affected by migraine with aura showed a linear relationship between copy number of the T allele carried by the individual and the age of migraine onset. Our data suggest that the PROGINS PGR polymorphism does not directly predispose to migraine but significantly delays migraine onset probably via a reduction in brain neuronal excitability.
    DNA and cell biology. 12/2014;
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    ABSTRACT: Several studies suggest a role of oxidative stress in the physiopathology of migraine, particularly in the form with aura. In a case-control study, we investigated the association between migraine and SOD1 and SOD2 genes in a cohort of 490 consecutive unrelated Caucasian migraineurs (migraine with aura - MwA n=107, migraine without aura - MwoA n=246 and chronic migraine - CM n=137) and 246 healthy controls recruited at our Headache and Pain Unit and stored in the Interinstitutional Multidisciplinary BioBank (BioBIM). Migraine phenotype was carefully detailed using face-to-face interviews. We examined polymorphisms of SOD1 gene (A/C substitution - rs2234694) and SOD2 gene (C/T transition - rs4880 - Ala16Val). The rs4880 TT (Val/Val) genotype was associated (P=0.042) with the presence of unilateral cranial autonomic symptoms (UAs) in MwA patients. We also found a mild correlation between SOD2 rs4880 genotype and the type of acute migraine treatment (P=0.048) in MwA patients. Our findings suggest that SOD2 is a disease-modifier gene influencing oxidative mechanisms in MwA. These observations lead to the hypothesis that SOD2 polymorphism may cause a defective control of the oxidative phenomena linked to cortical spreading depression, the neurophysiological hallmark of migraine aura, causing an overstimulation of trigeminal neurons and UAs triggering.
    Antioxidants & redox signaling. 10/2014;
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    ABSTRACT: Introduction: Ample evidence that nitric oxide (NO) is a causative molecule in migraine has encouraged research to develop drugs that target the NO-cGMP cascade for migraine treatment. NO synthase (NOS) inhibition is an innovative therapeutic principle. Areas covered: This paper reviews the rationale underlying NOS inhibition in migraine treatment. It also provides a review on the efficacy and safety data for NOS inhibitors (nonselective NOS inhibitor L-N(G)-methyl-arginine hydrochloride [L-NMMA], selective inducible NOS [iNOS] inhibitors GW273629 and GW274150, combined neuronal NOS [nNOS] inhibitor and 5-HT1B/1D receptor agonist NXN-188) in acute or preventive migraine treatment. Expert opinion: The data highlighted herein, from four placebo-controlled trials and 1 open-labeled clinical trial using 4 different NOS inhibitors on a total of 705 patients, provide convincing efficacy data only for the nonselective NOS inhibitor L-NMMA. Unfortunately, this NOS inhibitor raises cardiovascular safety concerns and has an unfavorable pharmacokinetic profile. As experimental studies predicted, iNOS inhibitors are ineffective in migraine. Still, upcoming selective nNOS inhibitors are a hope for migraine treatment, with the nNOS isoform being most clearly involved in trigeminovascular transmission and central sensitization. Future studies should help to clarify whether NOS inhibition is equally fruitful in acute and preventive treatment. It should also clarify if nNOS inhibition holds promise as a therapeutic tool for the treatment of chronic migraine and other forms of headache.
    Expert Opinion on Investigational Drugs 05/2014; · 4.74 Impact Factor
  • P Barbanti, G Egeo, C Aurilia, L Fofi
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    ABSTRACT: Tension-type headache (TTH) is the second most common human disease, accounting for intense disability, high costs and numerous workdays lost. Tension-type headache is less simple and easy-to-treat than commonly thought. Antidepressants, despite their poor tolerability, are still the first-choice drugs for preventing TTH. The most widely studied non-pharmacological approach to TTH, cognitive-behavioral techniques, effectively relieve pain only in selected patients. The most frequently used and recommended treatments for acute TTH, NSAIDs and paracetamol have scarce efficacy as documented by their low therapeutic gain over placebo in the 2-h pain-free response. Their effectiveness may be increased by a more proper use and by the adjunction of caffeine, antiemetics, myorelaxants or tranquillizers but the risk of medication-overuse headache must be considered. Hence, the need for more effective and tailored treatments in TTH remains.
    Neurological Sciences 05/2014; 35 Suppl 1:17-21. · 1.41 Impact Factor
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    ABSTRACT: Headache is one of the most common symptoms after cocaine use. We investigated headache frequency and characteristics and the correlation between headache and acute cocaine intake in a cross-sectional study in a consecutive series of chronic cocaine users. Participation rate was 94.1%. Of the 80 subjects enrolled, 72 (90%) reported current headaches, in most cases migraine or probable migraine without aura. Of these 72, 29 (40.3%) had a headache history, whereas 43 (59.7%) reported de novo headache after beginning to use cocaine. After acute cocaine use, a large percentage of users reported headache attacks: 86.2% of previous headache sufferers (migraine or probable migraine without aura in all cases) and 93% of de novo headache sufferers (migraine/probable migraine without aura = 35; episodic tension-type headache = three patients; cocaine-induced headache= two patients). Most subjects reported that when they used cocaine headaches worsened. Chronic cocaine use frequently seems to worsen or induce headache with migraine or migraine-like characteristics, probably owing to a serotoninergic and dopaminergic system impairment. In headache sufferers, especially those with migraine headaches, clinicians should enquire into possible cocaine use.
    Cephalalgia 02/2014; · 3.49 Impact Factor
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    ABSTRACT: Aim: In the present case-control study, we investigated the correlation between the common ACE insertion/deletion (I/D) polymorphism and migraine. Materials & methods: Genotyping of the ACE I/D variant was performed in 502 Caucasian patients with migraine and 323 age-, sex- and race/ethnicity-matched healthy controls. We investigated associations between ACE genetic variants and sociodemographic and/or clinical features of migraineurs. Results: We found a significant association between ACE insertion/insertion (I/I) polymorphism and lower use of pharmacological prophylaxis in migraine patients with aura and in those with chronic migraine. Moreover, ACE I/I polymorphism was significantly more common in migraine patients with aura who had a negative family history of migraine. Conclusion: Our data suggest that although the ACE I/D polymorphism is not a direct risk factor for migraine, the ACE I/I genotype may influence the clinical feature of this disease being associated with reduced use of prophylactic agents in patients with migraine with aura and in those with chronic migraine. Original submitted 5 June 2013; Revision submitted 16 September 2013.
    Pharmacogenomics 02/2014; 15(2):147-55. · 3.86 Impact Factor
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    ABSTRACT: Migraine pain is often preceded, accompanied and followed by dopaminergic symptoms (premonitory yawning and somnolence, accompanying nausea and vomiting, postdromal somnolence, euphoria and polyuria). After reviewing evidence from pharmacological, biochemical, genetic and animal experimental studies on the relationship between dopamine and migraine, and matching these data with patients' clinical features, we postulate that migraine attacks could be characterized by an ictal dopamine release in a subject with dopamine receptor hypersensitivity due to a chronic dopaminergic deficit synergistic to serotoninergic impairment. Our review suggests that when the attack begins, a low dopamine plasma concentration stimulates hypersensitive central presynaptic dopamine receptors thus causing prodromal symptoms such as yawning and somnolence. Increasing dopamine levels, though still insufficient to stop trigeminovascular activation, stimulate postsynaptic dopamine receptors thus inducing nausea, vomiting and hypotension. Finally, dopamine levels slowly return to baseline, giving rise to somnolence and fatigue, but, in some cases, continue to rise triggering postdromal symptoms such as euphoria and polyuria.
    Neurological Sciences 05/2013; 34 Suppl 1:67-70. · 1.41 Impact Factor
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    ABSTRACT: Prion protein, a sialoglycoprotein with neuroprotective properties on oxidative stress damage, has been related with the mechanisms leading to migraine. In the present case-control study, we investigated the correlation between the common methionine/valine polymorphism at codon 129 within the prion protein gene (PRNP) and migraine. Genotyping of PRNP V129M variant was performed in 384 migraine patients and 185 age-, sex-, and race-ethnicity-matched healthy controls. The frequencies of the PRNP V129M genotype did not differ significantly between migraineurs and controls. The frequencies of 129VV genotype were significantly higher in patients with earlier age at migraine onset. No correlation was found between PRNP 129 genotype and demographics, and other clinical migraine features. Our data suggest that the PRNP 129VV polymorphism is not a direct migraine risk factor but is significantly associated with an earlier onset of the disease.
    Headache The Journal of Head and Face Pain 02/2013; · 2.94 Impact Factor
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    ABSTRACT: The development of Biobanks and recent advances in molecular biology have enhanced the possibility to accelerate translational research studies. The Interinstitutional Multidisciplinary BioBank (BioBIM) is organized in a large healthy donors collection and pathology-based biobanks with the aim to provide a service for development of interdisciplinary studies. A new pathology-based biobank has been organized to specifically collect biospecimen from patients affected by migraine, with the final goal to centralize data, collect blood, plasma, serum, DNA and RNA of patients with this disease. The BioBIM is fully equipped for the automation of sampling/processing, storage and tracking of biospecimens. Standard Operating Procedures have been developed for processing and storage phases as well as archive of clinical data. The availability of biospecimens and clinical data will constitute a resource for various research projects.
    Neurological Sciences 01/2013; · 1.41 Impact Factor
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    ABSTRACT: BACKGROUND: Excessive daytime sleepiness is a major clinical and health concern that can have varied and sometimes harmful consequences. Findings from uncontrolled studies suggest a high prevalence in patients with chronic migraine. METHODS: In a case-control study, we compared frequency data for excessive daytime sleepiness in 100 patients with chronic migraine and 100 healthy controls paired for sex and age, and assessed risk factors including lifestyle, sleep quality, anxiety, depression, concomitant disease and medications. RESULTS: The frequency of excessive daytime sleepiness was higher in migraineurs (especially in those with medication overuse) than in controls (20% versus 6%; odds ratio 3.92, 95% CI 1.5-10.22), but was lower than previously reported and correlated with poor quality sleep and anxiolytic and antidepressant use. CONCLUSIONS: Again confirming that disability in chronic migraine is multifactorial in origin, excessive daytime sleepiness, especially in migraineurs who overuse medications, adds to the multiple factors known to impair social and working function. Patients with chronic migraine might benefit from diagnostic interviews focussing also on sleep problems and from targeted psychoactive drug prescribing.
    Sleep Medicine 01/2013; · 3.49 Impact Factor
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    ABSTRACT: Objective.- To clarify the frequency and characteristics of altered transverse sinus morphology in a series of consecutive patients with chronic migraine. Background.- As terminology, neuroradiological techniques and patient selection differ widely across various studies, reliable, reproducible information is lacking on the frequency of cerebral transverse sinus asymmetry as measured by cerebral magnetic resonance venography in patients with chronic migraine. Methods.- We assessed the frequency and characteristics of transverse sinus asymmetries and their correlation with the chronic migraine phenotype in a blind, cross-sectional magnetic resonance venographic study in a series of 83 consecutive patients with chronic migraine. Results.- After excluding mild (≤10%) physiological differences in transverse sinus diameter, we found magnetic resonance venographic evidence of altered transverse sinus morphology in 50.6% of the patients: 16.9% had moderate transverse sinus asymmetry (≤50%), 24.1% severe asymmetry (>50%), and 9.6% aplasia. Among the tested risk factors for migraine chronification, analgesic consumption, anxiety, and high systolic blood pressure were more frequent in patients with transverse sinus aplasia than in those without. Conclusions.- Advanced magnetic resonance venographic techniques used in strictly selected subjects disclose transverse sinus asymmetries in as many as 50.6% of patients with chronic migraine, even when mild differences in physiological caliber are excluded. The unexpected correlation between transverse sinus aplasia and some risk factors for migraine chronification requires confirmation in larger studies.
    Headache The Journal of Head and Face Pain 05/2012; 52(8):1254-61. · 2.94 Impact Factor
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    ABSTRACT: Migraine prevention hinges on a variety of non-specific drugs that mainly reduce neuronal hyperexcitability, the putative pathophysiological hallmark for migraine. The improved knowledge about migraine circuitry and neurobiology has prompted research to develop new specific migraine preventive medications targeted to innovative sites and mechanisms. Drugs designed to inhibit cortical spreading depression, for example tonabersat, might offer a useful option for the management of migraine with aura but not for migraine without aura. Inducible nitric-oxide synthase (iNOS) inhibition seems ineffective as a prophylactic strategy. Results are awaited from recent and ongoing phase II trials with glutamate receptor antagonists, third-generation antiepileptics, melatonin agonists, vitamin D3 and statins.
    Neurological Sciences 05/2012; 33 Suppl 1:S137-40. · 1.41 Impact Factor
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    ABSTRACT: The objective and background is to confirm in a double-blind, placebo-controlled study the high triptan response rates we had previously reported in an open study in migraine patients with unilateral cranial autonomic symptoms. In this randomized, double-blind, placebo-controlled study 80 migraineurs with unilateral cranial autonomic symptoms were assigned to receive rizatriptan 10 mg wafer or placebo (ratio 1:1) and treated for a single moderate or severe migraine attack. The primary endpoints were pain freedom at 2 h and total migraine freedom at 2 h. Secondary endpoints included pain relief, no associated symptoms and sustained pain freedom or relief. Significantly more patients reported pain freedom at 2 h after taking rizatriptan (54 %) than after placebo (8 %) (therapeutic gain 46 % [28 %; 64 %]; P < 0.001). Similarly, significantly more patients reported total migraine freedom at 2 h after rizatriptan (51 %) than after placebo (8 %) (therapeutic gain 43 % [26 %; 61 %]; P < 0.001). Rizatriptan was also more effective than placebo on most secondary endpoints. We confirm in a placebo-controlled study our previous data suggesting that the presence of unilateral cranial autonomic symptoms in migraineurs predicts a positive response to triptans, probably owing to intense trigeminal peripheral afferent activation which strongly recruits peripheral neurovascular 5-HT1B/1D receptors. Acute and preventive pharmacological trials in migraine should focus also on this subset of migraine patients.
    The Journal of Headache and Pain 03/2012; 13(5):407-14. · 2.78 Impact Factor
  • P Barbanti, C Aurilia, G Egeo, L Fofi
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    ABSTRACT: A wide array of options are now available for migraine prophylaxis. Conventional treatments include beta-blockers, anticonvulsants, antidepressants, calcium antagonists and antiserotoninergic drugs. Emerging medications such as ACE inhibitors, sartans and nutritional supplements are gaining favour for migraine prophylaxis. Botulinum toxin type A is a promising therapeutic tool for chronic migraine. Tonabersat is likely to be a step forward for the treatment of migraine with aura. However, much work is needed to identify predictive clinical features of successful responsiveness and to better define the duration of prophylaxis.
    Neurological Sciences 05/2011; 32 Suppl 1:S111-5. · 1.41 Impact Factor
  • P Barbanti, C Aurilia, G Egeo, L Fofi
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    ABSTRACT: Progression of episodic migraine to chronic migraine may be related to comorbid medical conditions. In this study, we focused on the role played by arterial hypertension in migraine transformation. Several studies reveal that hypertension is associated with chronic migraine and may induce migraine chronification. Hypertension probably amplifies the effects of migraine on the vascular wall further enhancing the endothelial dysfunction in cerebral vasculature. Consequently, monitoring of blood pressure is recommended in migraineurs showing an otherwise unexplained increase in attack frequency. Studies are needed to verify if prophylactic treatment with drugs improving endothelial function (e.g. calcium channel blockers, beta blockers, calcium inhibitors, ACE inhibitors and sartans) may selectively ameliorate the course of migraine in these patients.
    Neurological Sciences 06/2010; 31 Suppl 1:S41-3. · 1.41 Impact Factor
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    ABSTRACT: Essential tremor (ET) and migraine headache are considered comorbid diseases on the basis of uncontrolled studies. We investigated the frequency of migraine in patients with ET by enrolling 110 patients with ET and 110 age- and sex-matched healthy controls in a case-control study. We found no significant differences in the frequency of lifetime and current migraine between patients and controls, even in patients stratified for age. Tremor had similar clinical features in patients with ET with and without migraine except that females predominated in patients with ET and migraine. Migraine also had similar characteristics in both patients with ET and migraine and in controls with migraine. Our study excludes a comorbid association between ET and migraine. When ET and migraine coexist their clinical phenotype and evolution remain almost unchanged.
    Cephalalgia 06/2010; 30(6):686-9. · 3.49 Impact Factor
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    ABSTRACT: To find out more about glutamatergic and gabaergic transmission in migraine, in this study we investigated glutamate-dependent short-term synaptic potentiation and GABA-dependent inhibitory cortical interneuron excitability as assessed by 5Hz-rTMS delivered over primary motor cortex (M1) (motor evoked potential, MEP, amplitude facilitation and cortical silent period, CSP, duration lengthening) in migraine patients with (MA) and without aura (MwoA) and healthy controls. We studied 37 patients with migraine (19 MA and 18 MwoA) and 19 healthy control subjects. 5Hz-rTMS was delivered at 120% resting motor threshold to the hand motor area of the left hemisphere with the target muscle at rest and during contraction. Three of the MA patients were also tested at the end of visual aura during a spontaneous migraine attack. ANOVA showed that the MEP significantly increased in size and CSP significantly lengthened during 5Hz-rTMS in the three groups tested. The 5Hz-rTMS-induced MEP facilitation differed significantly being highest in MA patients. In the three patients tested both ictally and interictally the MEP increased during the interictal session but remained unchanged when the visual aura ended. Our study shows that the neurophysiological feature that differentiates MA patients from MwoA patients and healthy controls is an abnormal M1 susceptibility to 5Hz-rTMS both outside and during the attack suggesting that glutamate-dependent short-term M1 cortical potentiation patterns differ in migraine with and without aura.
    Pain 10/2009; 148(1):43-8. · 5.64 Impact Factor
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    ABSTRACT: Our objective was to report the clinical characteristics and to investigate the role of SLITRK1 gene in a large Italian family with Tourette syndrome (TS). The diagnosis of TS and chronic motor tics (CMT) was made according to "The Tourette Syndrome Classification Study Group" (1993). Psychiatric diagnoses were made by administering the Structured Clinical Interview for DSM and the Yale-Brown Obsessive Compulsive Scale. Genetic study included direct sequencing and copy number analysis of the SLITRK1 gene, and haplotype analysis. We found tics or other behavioral manifestations in 15 subjects. Of these, 5 received a diagnosis of definite TS, 5 were classified as having definite CMT, 2 had definite nonspecific tic disorder, and 3 patients had obsessive-compulsive disorder without motor or phonic tics. Tics mainly involved the craniocervical district. Many patients with tics had coexisting psychiatric disorders, especially obsessive-compulsive disorder, performed poorly at school and had social problems. Direct sequencing and copy number analysis of the SLITRK1 gene, and haplotype analysis suggested that the SLITRK1 locus was not involved in this family. In conclusion, the distinctive clinical features in this family are the motor tics mainly involving the face and the neck and the severe coexisting psychiatric disorders. The negative results of the SLITRK1 analysis point to genetic heterogeneity in TS.
    Movement Disorders 12/2007; 22(15):2229-34. · 4.56 Impact Factor
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    ABSTRACT: Migraine patients often complain of sleepiness, a problem that manifests both during and outside an attack, may impair the quality of life and can lead to potentially harmful situations. Findings from an uncontrolled study suggest that a high percentage of migraineurs experience excessive daytime sleepiness (EDS). We investigated EDS in a case-control study on 100 patients with episodic migraine and 100 age- and sex-matched healthy controls and also assessed sleep quality, anxiety and depression. Although it was found that EDS was more frequent in migraineurs than in controls (14% vs. 5%; odds ratio 3.1; 95% confidence interval 1.1-8.9), the frequency was lower than previously reported. EDS correlated with migraine disability, sleep problems and anxiety. EDS in patients with migraine probably stems from the full constellation of headache-sleep-affective symptoms resulting from the complex clinical burden of the disease.
    Cephalalgia 11/2007; 27(10):1115-9. · 3.49 Impact Factor
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    ABSTRACT: Excessive daytime somnolence (EDS) and quality of sleep were studied in 25 parkinsonian patients at baseline, when they had not yet received any antiparkinsonian medication, and after 1 year of treatment with dopaminergic drugs. EDS was measured by the Epworth Sleepiness Scale (ESS) and sleep quality by the Pittsburgh Sleep Quality Index (PSQI). At baseline, the ESS score was not different from that of age-matched healthy controls. The mean ESS score increased significantly after 1 year of follow-up, being more than 10 in 12 patients. The mean PSQI also increased significantly after 1 year of treatment, but there were no differences in the number of "bad sleepers" at baseline and at follow-up. In conclusion, EDS seems to emerge during the course of the illness, at least in a proportion of PD patients, and could represent another clinical correlate of the interaction between the ongoing neurodegenerative process and the side effects of drugs.
    Neurological Sciences 11/2003; 24(3):178-9. · 1.41 Impact Factor

Publication Stats

222 Citations
64.97 Total Impact Points

Institutions

  • 2010–2011
    • Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana
      Roma, Latium, Italy
  • 2001
    • Sapienza University of Rome
      • Department of Anatomical, Histological, Forensic Medicine and Orthopedic Science
      Roma, Latium, Italy