Efficacy in high frequency migraine with aura prevention of a combination of Tanacethum Parthenium, 5 - hydroxy tryptophan
and magnesium (Aurastop©)
Giorgio Dalla Volta, Paola Zavarise, Gaelle Ngonga, Danilo Fontana Headache Center of Neurological Unit of Istituto Clinico Citta' di Brescia, Brescia
Correspondence:Giorgio Dalla Volta ([email protected]) The Journal of Headache and Pain2018,19(Suppl 1):P176
Background: Each component of the novel phytotherapic combin-
ation of Tanacethum Parthenium (150 mg), 5-hydroxy tryptophan (20 mg) and magnesium (185 mg) (Aurastop©) acts on a different target among the main mechanisms involved in the pathophysiology of mi- graine and of the aura itself : sensitization of trigeminal vascular sys- tem, central sensitization and activation of the "migraine generator" located in the brainstem, through glutammate and kynurenine path- ways and the cortical spreading depression [1,2,3]. Aim of this study is to test the effectiveness of Aurastop©in the prophylaxis of mi- graine with aura with high frequency
Materials and methods: 18 patients (F: n=10, M: n=8, mean age: 28 )
presenting with an ICHD-3 beta diagnosis of migraine with aura (MWA ) with a frequency of more than 5 attacks of migraine with aura per month since at least 6 months, were enrolled in the survey and treated with Aurastop©twice a day for a period of 3 months. Diary cards were filled in during a 3-months period prior the begin- ning of the survey and during the 3-months duration of the study. The reduction of MWA attacks per month was assessed as the pri- mary end-point; the reduction of the duration and disability of the aura and of the intensity of the headache were considered as sec- ondary end-points.
Results: A statistically significant reduction of MWA attacks /month was observed: more than 95% of the patients referred a reduction >50% of the frquency. Moreover, a sensible reduction of the duration and disability of the aura phenomena was reported by more than 90% of the patients and, in the 60% of the patients also a reduction of the intensity of the headache. No side effects were reported. The efficacy started to appear during the first month of intake and was maintained during the three months of therapy .
Conclusion: In this observational open study, Aurastop©appears to
be effective and safe as a preventive treatment of MWA in the pa- tients with a high frequency of attacks.
References
1. Curto M, Lionetto L, Negro A, Capi M, Fazio F, Giamberardino MA, Simmaco M, Nicoletti F, Martelletti P. Altered kynurenine pathway metabolites in serum of chronic migraine patients. J Headache Pain. 2015; 17: 47.
2. Geppetti P, Bernabei S, De Cesaris F. CGRP receptors and TRP channels in migraine. J Headache Pain. 2015; 16(Suppl 1): A21.
3. Diener HC, Pfaffenrath V, Schnitker J, Friede M , Henneicke-von Zeppelin HH. Efficacy and safety of 6,25 mg t.i.d feverfew CO2-extract ( MIG-99) in migraine prevention–a randomized , double blind, multicenter, placebo controlled study. Cephalalgia. 2005; 25: 1031-41.
P177
Quantitative analysis of perfusion Computed Tomography images increases the evidence of hypoperfusion during migrainous aura
Laura D’Acunto1, Antonio Granato1, MilošAjčević1, Giovanni Furlanis1, Maja Ukmar2, Irene Zorzenon2, Mariana Ridolfi1, Paolo Manganotti1 1Department of Medical, Technological and Translational Sciences, Headache Centre, University of Trieste, Italy;2Department of Radiology, Cattinara Hospital, University of Trieste, Italy
Correspondence:Laura D’Acunto ([email protected]) The Journal of Headache and Pain2018,19(Suppl 1):P177
Background:Perfusion computed tomography (PCT) represents a rapid
and practical technique for assessment of salvageable tissue and infarct core in acute stroke imaging [1,2]. Perfusion patterns found during mi- graine with aura are controversial, in fact normal, hypo- and hyperper- fusion were reported, though perfusion measurements were not always performed in the acute phase of the aura [3-6]. Aim of the present study is to demonstrate that an ad hoc quantitative analysis of PTC images may detect perfusion anomalies in migrainous aura that are not highlighted in the routine PCT images analysis.
Patients and Methods:Patients who presented a focal neurological def- icit compatible with migraine with aura were enrolled. All the patients performed PTC during migrainous aura and no perfusion abnormality was found at first visual assessment. For each patient, a cerebral region of interest (RoI) was placed by two blinded neuro-radiologists according to the symptoms of the patient. As MTT maps are the most reliable in analysis of hypoperfusion [7], a quantitative analysis of mean transit time (MTT) maps on the RoI, voxel per voxel, by a semi-automatic algorithm was made. Data were compared with the mirrored RoI in the unaffected hemisphere (mRoI) (Fig. 1). Demographic data, characteristics of head- ache, and asymmetry of MTT between RoI and mRoI [ΔMTT=(MTT RoI– MTT mRoI)/MTT mRoI*100)] were evaluated. Each patient provided a writ- ten consent that allowed the analysis of data for research purposes. Results:Six patients were enrolled (4 F, 2 M, mean age 43±23 y). PTC was performed after 70±15 minutes from symptoms onset. All patients were migraineurs, two of them already suffered with migraine with aura. Characteristics of migrainous aura are shown in Table 1, 50% of patients had headache at the onset of aura. In all patients, MTT values increased in RoI compared to mRoI (meanΔMTT=19.9% [1.8-60.4%]), without effect of time of PTC performance (Table 1).
Conclusions:An ad hoc quantitative analysis of PTC images during mi- grainous aura detects an increase of MTT in cerebral RoI that corre- sponds to hypoperfusion that was not highlighted in the routine PCT images analysis. The use of this quantitative analysis in clinical practice can reduce the percentage of migrainous aura false negatives.
References
[1] Krishnan P, Murphy A, Aviv RI. CT-based Techniques for Brain Perfusion. Top Magn Reson Imaging. 2017;26(3):113-119.
[2] Furlanis G, Ajčević M, Stragapede L, et al. Ischemic Volume and Neurological Deficit: Correlation of Computed Tomography Perfusion with the National Institutes of Health Stroke Scale Score in Acute
Table 1 (abstract P175).CTE
Ischemic Stroke. J Stroke Cerebrovasc Dis. 2018. Doi:10.1016/ j.jstrokecerebrovasdis.2018.04.003
[3] Nieuwkamp DJ, van der Schaaf IC, Biessels GJ. Migraine aura presenting as dysphasia with global cognitive dysfunction and abnormalities on perfusion CT. Cephalalgia 2010;30:1007-9.
[4] Hansen JM, Schytz HW, Larsen VA, Iversen HK, Ashina M. Hemiplegic Migraine Aura Begins With Cerebral Hypoperfusion: Imaging in the acute phase. Headache, 2011;51:1289-1296.
[5] Shah L, Rana S, Valeriano J, Scott TF. Reversible CT perfusion abnormalities in patient with migraine variant: a two phase process. Clin Neurol Neurosurg. 2013;115(6):830-832
[6] Ridolfi M, Granato A, Polverino P, et al. Migrainous aura as stroke-mimic: The role of perfusion-computed tomography. Clin Neurol Neurosurg. 2018;166:131-135
[7] Floery D, Vosko MR, Fellner FA, et al. Acute-onset migrainous aura mim- icking acute stroke: MR perfusion imaging features. AJNR Am J Neurora- diol. 2012;33(8):1546-1552
P178
Cerebello-thalamo-cortical inhibitory activity impairment in patients with chronic migraine
Gianluca Coppola1, Clarissa Elizabeth Centurioni1, Chiara Abagnale1, Vincenzo Maria Parisi2, Mariano Serrao1, Cherubino Di Lorenzo3, Francesco Pierelli1,4
1Sapienza University of Rome Polo Pontino, Department of Medico- Surgical Sciences and Biotechnologies, Latina, Italy;2G.B. Bietti Foundation IRCCS, Research Unit of Neurophysiology of Vision and Neurophthalmology, Rome, Italy;3Don Carlo Gnocchi Onlus Foundation, Milan, Italy;4IRCCS-Neuromed, Pozzilli (IS), Italy
Correspondence:Gianluca Coppola ([email protected]) The Journal of Headache and Pain2018,19(Suppl 1):P178
Background
Chronic migraine (CM) patients with or without medication overuse often present structural changes within the cerebellum. In healthy humans, the cerebellum exerts a suppressive effect on the contralat- eral motor cortical response, through a cerebello-thalamo-cortical pathway. Here, we investigate the cerebello-thalamo-cortical func- tioning in patients affected from chronic migraine.
Materials and methods
We recruited 19 patients affected from CM (11 without and 8 with medication overuse), and we compared them to a group of 18 healthy volunteers (HVs). After a conditioning single pulse high- voltage electrical stimulation delivered over the posterior surface of the mastoid processes (anode placed on the right side, and the cath- ode on the left), a TMS pulse was delivered over the contralateral motor cortex with 5, 7, 10, and 15 ms interstimulus interval (ISI) in random order. Five stimuli were delivered at each ISI. Motor cortical excitability changes were evaluated by amplitude changes of EMG responses from the first dorsal interosseous muscle to motor cortical stimulation. Furthermore, we have tested correlations of neuro- physiological parameters with CM clinical features.
Results
In HVs, suppression occurs at an ISI of 5 ms (-19.4%) and lasts a few milliseconds. In CM patients, conditioning electric stimulation over the cerebellum did not reduce the size of MEPs to test TMS of the motor cortex at conditioning-test intervals of 5 ms (+3.0%, p=0.022). In CM patients, the percentage of MEP suppression at 5 ms ISI negatively correlated with number of tablets taken per month (r= -0.473, p= 0.04).
Conclusions
We found neurophysiological evidence for cerebello-thalamo-cortical inhibitory pathway malfunctioning in CM, a chronic head pain condi- tion where an abnormal structure of the cerebellum had been previ- ously reported. Overall, we reason that abnormal macrostructural and functional patterns in the cerebellum might be involved in cue- elicited acute medication craving. Whether these functional abnor- malities are due to primary abnormal cerebellar inhibitory dysfunc- tion or are secondary to a disrupted cerebellar-thalamic-cortical connectivity, remains to be determined.
P179
Transcranial direct current stimulation as add-on therapy in the detoxification of patients with chronic migraine and medication overuse headache: clinical and EEG findings
Roberto De Icco1,2, Cristina Tassorelli1,2, Irene De Paoli1, Raffaele Manni3, Michele Terzaghi3, Riccardo Cremascoli2,3, Giorgio Sandrini1,2, Grazia Sances1
1
Headache Science Center, IRCCS Mondino Foundation;2Department of Brain and Behavioral Sciences, University of Pavia;3Unit of Sleep Medicine and Epilepsy, IRCCS Mondino Foundation
Correspondence:Roberto De Icco ([email protected]) The Journal of Headache and Pain2018,19(Suppl 1):P179
Fig. 1 (abstract P177).Perfusion Computed Tomography (Mean
Transit Time images) performed during migrainous aura of the six patients. Circles with red arrows= symptomatic area; circles without red arrows= unaffected control area. Symptomatic area size= 1470 voxel
Table 1 (abstract P177).Clinical features of the six patients with migrainous aura
Patients Age Gender History of migraine Symptoms Headache at the onset of symptoms NIHSS Time to PTC after symptoms onset Symptoms duration Δ MTT (%) 1 52 F Yes, without aura Right hemiparaestesia and dysphasia
Yes 2 60 min 2 hours 1,8
2 83 F Yes,
with aura
Aphasia Yes 4 60 min 2 hours 13
3 49 F Yes, without aura left hemiparesis left sensitive- motor No 3 90 min 2 hours 8,4 4 28 M Yes, with aura hemisyndrome and left homonymous hemianopsia No 7 90 min 24 hours 30,2 5 21 M Yes, without aura
Aphasia Yes 1 60 min 2 hours 60,2
6 26 F Yes,
without aura
left hemiparesis No 3 60 min 10 hours 6,1
Objectives: Transcranial direct current stimulation (tDCS) has been tested with encouraging results in the management of different pain- ful conditions such as fibromyalgia, trigeminal neuralgia, and migraine.
Chronic migraine with medication overuse (CM+MO) represents a challenging condition where discontinuation of overused drugs is ef- fective in a fairly high percentage of patients, but burdened by re- lapse into the previous situation.
The aim of this study is to evaluate the efficacy of anodic tDCS as an add-on therapy to the conventional treatment in patients with CM +MO.
Methods: We enrolled twenty patients (16 females, age range 32-65)
with CM+MO among those hospitalized at the C. Mondino Founda- tion of Pavia for a detoxification program. They were randomly assigned to 2 groups: subjects in the tDCS-Group underwent 5 daily sessions of anodic tDCS on motor primary area M1 (contralateral to the most affected side of pain or on the right side in case of bilateral pain); subjects in the Sham-Group underwent 5 daily sessions of sham stimulation.
Patients underwent EEG recordings immediately before and after the first session of tDCS (T0 and T1), immediately before and after the fifth session of tDCS (T2 and T3) and 1 month later (T4).
Results: The two study groups were comparable at baseline. In the
tDCS-Group we found a significant reduction in the number of head- ache days/month, days and drug doses/month at T4 when compared to baseline (p=0.001, p=0.001, p=0.002, respectively). In the Sham- Group, only the reductions in days and drug doses/month were sig- nificantly reduced at T4 (p=0.002 and p=0.001, respectively). Indeed the number of headache days /month at T4 was significantly lower in the tDCS-Group respect to Sham-Group (p=0.032). The percentage of patients with a 50% or more reduction in headache days/month at T4 was 70% in the tDCS-Group and 12.5% in the Sham-Group (p=0.025).
As regards EEG data, we observed an increase in the alfa power spectrum in the tDCS-Group in the occipital and frontal regions. This increase was significant at T1 and T3 when compared to T0 and it was also significantly more marked when compared to Sham-Group at T1, T2 and T3.
Conclusion: Our findings suggest the clinical efficacy of anodic tDCS as an add-on to a detoxification protocol in patients with CM+MO. The observed potentiation of alfa rhythm after anodic tDCS may be explained by the clinical improvement, however it is tempting to hypothesize that it could reflect a modulatory effect on the pain matrix.
P180
Ultrasound biomicroscopy detects secondary hemicrania continua attributed to hidden narrow angle glaucoma
A. Granato, A. Dinoto, C. Bertolotti, D. Stokelj, L. Antonutti, P. Manganotti Department of Medical, Technological and Translational Sciences, Headache Centre, University of Trieste, Italy
Correspondence:A. Granato ([email protected]) The Journal of Headache and Pain2018,19(Suppl 1):P180
Background
Hemicrania continua (HC) is coded in ICHD-3 as a primary headache in the Trigeminal Autonomic Chephalalgias. Although many ophtal- mological conditions may be related to HC, no case of secondary HC attributed to narrow angle glaucoma has been described yet. Case report
A 39-years old Caucasian woman with history of low frequency mi- graine without aura accessed to the Emergency Department (ED) for the sudden onset of right frontal and retro-orbital continuous head- ache, with 6-7 daily exacerbations, which were associated with omo- lateral ptosis and lacrimation. Head CT scan was normal. Neurological examination evidenced right eyelid ptosis and conjunctival injection during pain exacerbations (Fig. 1). Because of unresponsiveness to analgesics, she was admitted to the Neurology Unit. Prednisone, Ver- apamil, Acetaminophen, transdermic Fentanyl and Diazepam were not effective. HC was suspected and intravenous Indomethacin 50
mg four times a day was started with only partial reduction of the in- tensity of continuous pain and of the number of daily exacerbations. Topiramate and Celecoxib were also added with no significant effect. During the hospitalization, the patient reported a slight loss of visual acuity in right eye. Therefore she performed brain MRI, ocular tonom- etry, fundoscopic examination and visual evoked potential which were normal. To rule out intermittent glaucoma, an ultrasound bio- microscopy was performed and bilateral narrowing of anterior cham- ber due to plateau iris was found. She was treated with bilateral YAG-laser iridotomy and she markedly improved. Continuous head- ache with neurovegetative symptoms and daily exacerbations disap- peared (Fig. 1). Prophylactic therapy was then slowly interrupted. At a fourth-month follow-up visit she complained only her usual epi- sodic migraine she already suffered.
Conclusions
Ultrasound biomicroscopy may be a useful and safe tool to detect hidden narrow angle glaucoma as a possible cause of secondary hemicrania continua, when fundoscopic examination and ocular to- nometry are normal.
Consent for publication: The patient provided a written consent that allowed the analysis of data and images for research purposes.
P181
Analysis of Injection Site Reactions across Four Placebo Controlled Trials of Erenumab for Migraine Prevention
Julio Pascual1, David Dole
žil2, Brendan Davies3, Hernan Picard4, Frank Hong5, Feng Zhang4, Fei Xue4, Dan Mikol4, Jan Klatt5
1Service of Neurology, University Hospital Marqués de Valdecilla and IDIVAL, Santander, Spain;2DADO MEDICAL sro, Prague Headache Center, Prague, Czech Republic;3Department of Neurology, Royal Stoke University Hospital, Stoke-on-Trent, UK;4Amgen Inc., Thousand Oaks, CA, USA;5Novartis Pharma AG, Basel, Switzerland
The Journal of Headache and Pain2018,19(Suppl 1):P181
Presented by Laura Bartolini – Medical Department Novartis Farma,
Italy
Objective:To assess the frequency of injection site reaction-related adverse events (ISR-AEs) observed in erenumab clinical trials in sub- jects with either episodic or chronic migraine.
Background Erenumab is a fully human monoclonal antibody that
selectively inhibits the calcitonin gene-related peptide (CGRP) recep- tor and is under investigation for migraine prevention.
Design/MethodsData were obtained from four randomized, placebo-
controlled trials (clinicaltrials.gov: NCT01952574, NCT02066415/ NCT02174861, NCT02456740, and NCT02483585). Analysis was per- formed for the 12-week double-blind placebo-controlled treatment period (DBTP; erenumab and placebo) and the entire erenumab expos- ure period (EEP), including the open-label extension phase (erenumab Fig. 1 (abstract P180).Right eyelid ptosis and conjunctival injection during pain exacerbations (a); normal eyes after bilateral YAG-laser iridotomy (b)
only). AEs were graded according to the Common Terminology Criteria Version 4.03. The studies were approved by national Competent Authorities.
ResultsOver the 12-week DBTP, incidence of ISR-AEs was 3.2%, 5.6%,
and 4.5% in the placebo, erenumab 70 mg, and 140 mg groups, re- spectively. Incidence of injection site pain, erythema and pruritus was comparable in the placebo, erenumab 70 mg, and erenumab 140 mg groups. Over the EEP, which extended erenumab exposure to median 46 weeks (mean 47 weeks, range 0–159), incidence of ISR- AEs was 6.1% and 4.2% in the erenumab 70 mg and 140 mg groups, respectively. Most ISR-AEs were mild (Grade 1). Moderate ISR-AEs (Grade 2) were injection site erythema (n=4, 0.2%), injection site pain (n=3, 0.1%), and injection site reaction, injection site induration, and injection site urticaria (n=1 each, <0.1%). There were no ISR-AEs of Grade >2, and no serious ISR-AEs. Across 2519 subject-years of ere- numab exposure, one subject discontinued due to injection site pain, one due to injection site rash, and one due to injection site urticaria. ConclusionISR-AEs occurred in a small proportion of subjects treated with either dose of erenumab, with little change over time. Most ISR- AEs were mild and did not require discontinuation.
Acknowledgements
This study was supported by Amgen Inc. This study has been first presented at the 70th Annual American Academy of Neurology Meeting (Los Angeles, 21-27 April, 2018).
P182
"Fusion Imaging”to identify Periaqueductal Gray Matter (PAG) in a Medication Overuse Headache (MOH) patient
Elena Guaschino1,2, Natascia Ghiotto1,2, Cristina Tassorelli2,3, Ana Bacila4, Daniele Bosone1, Grazia Sances2
IRCCS Mondino Foundation, Pavia;1Neurovascular Ambulatory, Clinical Neurophysiology Unit;2Headache Science Centre;3Department of Brain and Behavioral Sciences, University of Pavia, Italy;4Neuroradiology Department
Correspondence:Elena Guaschino; Natascia Ghiotto ([email protected])
The Journal of Headache and Pain2018,19(Suppl 1):P182
Background
The image fusion process is defined as gathering all the important information from multiple images and their inclusion into fewer im- ages, usually a single one, that is more informative than any single source image. Fusion techniques allow direct and immediate com- parison of ultrasound images with previously recorded radiological images.
The use of this technique in Neurosonology is recent and two authors have applied it to describe and identify intracranial vessels (1). Transcra- nial B-mode sonography (TCS) of brain parenchyma is increasingly used as a diagnostic tool for diagnosis and treatment monitoring of neuro- logical diseases, particularly movement disorders.
In our Neurosonology Unit in collaboration with the Headache Sci- ence Centre, we evaluate the reproducibility of digitized TCS image