Le reti neuronali del dolore nel paziente emicranico

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1 Le reti neuronali del dolore nel paziente emicranico Antonio Russo Ambulatorio del paziente con cefalee ed algie facciali Clinica Neurologica II Seconda Università degli Studi di Napoli Centro Cefalee Istituto Diagnosi e Cura Hermitage Capodimonte Napoli

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6 We sought to take advantage of the spatial and temporal resolution of whole brain event-related BOLD fmri to study in migraine pts: functional integrity of the pain matrix functional reorganization of anti-nociceptive pathways even in interictal periods correlation of such alterations with clinical parameters representing disease severity (disease duration, frequency etc )

7 16 Patients with episodic MwA ICHD-II criteria without hypertension, diabetes mellitus, heart disease, other chronic systemic diseases, stroke, substance abuse, other neurological, chronic pain or psychiatric disorders (HAM-A, HAM-D, M.I.N.I) migraine-free (-3 days and +7 days MRI scan) not taking any medications commonly prescribed for migraine prevention or attack medication (until -3 days MRI scan) MIDAS (MIgraine Disability Assessment Scale) and HIT-6 (Headache Impact Test) 16 healthy controls age and sex matched without hypertension, diabetes mellitus, heart disease, other chronic systemic diseases, stroke, substance abuse, other neurological, chronic pain or psychiatric disorders (HAM-A, HAM-D, M.I.N.I)

8 Signa 3T GE - TR: 1500 ms - TE: 32 ms - FOV: 24 mm - matrix 64x64 - flip angle: 90º - slice thickness: 5.0 mm - gap interslice: 0 fmri Data analysis - Brain voyager - Head movement correction, spatial normalization and smoothing with 6 mm FWHM - General Linear model (box-car design convolved with haemodynamic response function) - Random effects analysis (p<0.05 corrected)

9 CHEPS: Contact Heat Evoked Potential Stimulator fmri compatible short thermal stimuli (600ms) were applied to the maxillary skin tested only the side of the face more frequently affected during migraine attacks hot-non painful stimulation at 41 C (Katherine Roberts et al., 2008) painful heat at 51 (Moulton et al 2008) and 53 C degrees (Katherine Roberts et al., 2008) Numerical Rating Scale (M. Burgmer et al., 2010) 41 C 51 C 53 C R A N D O M

10 Patients mean±sd Controls mean±sd Sex 8M / 8F 8M / 8F Mean age y.o y.o. Mean disease duration years N.A. Frequency/month N.A. MIDAS N.A. HIT N.A. Main pain intensity (VAS) N.A. HAM-A HAM-D Side of pain 8R / 8L N.A. Side of stimuli 8R / 8L 8R / 8L

11 41 MAIN effect of stimuli (16 pts + 16 ctl) p < 0.05 corrected 41 C C C

12 Anterior cingulate cortex A B C Patients > Controls Bilateral somatosensory cortex C R Controls > Patients

13 A Patients > Controls 51 C B Pons R Controls > Patients 53 C

14 Numerical Rating Scale M. Burgmer et al. J Neural Transm (2010) Patients Controls p value R 41 C 3,75 + 3,16 3,66 + 2,38 p= 0.47 R 51 C 5,91 + 2, ,44 p= 0.46 R 53 C 7,41 + 2,23 8,41 + 1,31 p= 0.09

15 Results (4b): Group BY Stimulus Interaction (brainstem)

16 preserved integrity of the pain matrix in MwA interictal functional reorganization of cortical and sub-cortical areas in patients with MwA during processing of painful stimuli the brainstem divergent activation between MwA and controls positively correlate with clinical parameters such as frequency, pain intensity and disability.

17 RS-fMRI allows the study of brain functional connectivity at rest no tasks dependent (Raichle ME et al. 2001) In the last decade, several studies have evaluated the integrity of RS-networks in normal aging and different neurodegenerative disorders (Grecius MD et al. 2004; Damoiseaux JS et al. 2008; Galvin et al. 2011) To our knowledge no RS-fMRI studies have been conducted in patients suffering from migraine

18 Resting State Network (RSN) Default mode network associated with internal processing Executive network mediating goal-directed stimulus-response selection Visual network dedicated to visual processing Auditory network corresponding to the auditory-phonological system Sensory-motor network associated with sensorymotor processing Medial ventralprefrontal network related to self-referential mental activity

19 Functional connectivity BOLD response x[t] x y x y[t] y When two regions are functionally connected the local fmri signals (X and Y) are temporally correlated (Raichle ME et al. PNAS 2001)

20 EXECUTIVE-ATTENTION NETWORK DYSFUNCTION IN EPISODIC MIGRAINE WITHOUT AURA A. Russo, A. Tessitore, A. Giordano, L. Marcuccio, M. De Stefano, F. Salemi, D. Corbo, R. Conforti, F. Esposito, G. Tedeschi Cognitive deficits have been reported both during and between migraine episodes (O Bryant et al., 2005) Neuropsychological studies has revealed impaired performance in migraine pts - psychomotor speed and attention (Hooker et al., 1986; Calandre et al., 2005) - executive functioning (Mongini et al., 2005) A neuropsychological study remark the evidence of mild executive dysfunction in the interictal phase of MwoA and emphasize the role of subcortical white matter lesions in the disruption of prefronto-cerebellar loop in MwoA patients (Camarda et al., 2007) A PET study showed that migraine patients had significant hypometabolism in several areas such as Prefrontal Cortex and Anterior Cingulate Cortex (Kim et al., 2010)

21 Neuropsychological evaluation in MwoA patients mean SD Normal cut-off * Education (years) Global general cognition MMSE > 26/30 Psychiatric symptoms HARS < 14 HDRS < 10 Neuropsychological test TMT A TMT B WCST categories WCST err. perseveration WCST err. n. perseveration PF FAB

22 fmri results

23 Executive Network (Patients < Controls) R. Middle frontal gyrus R. Dorsal Anterior Cingulate Cortex

24 Discussion MwoA patients without executive dysfunction, in the interictal period, showed significant regional differences in distribution of executive-mode network components. There were no correlations between disturbances of FPN functional connectivity and clinical features such as age of disease onset, disease duration, frequency (day/month) and duration of migraine attack. Nevertheless, post-hoc analyses revealed that functional connectivity in the MFG was negatively correlated with the intensity of pain of migraine attacks (i.e. the higher the pain intensity, the lower the functional connectivity within FPN).

25 Neuropsychological evaluation L. Marcuccio Patients recruitment A. Giordano F. Conte F. d Onofrio proudly made in Napoli fmri data analysis A. Tessitore F. Esposito MRI data aquisition G. Taglialatela A. Paccone The Bosses J G. Tedeschi V. Bonavita

Supplementary Information Methods Subjects The study was comprised of 84 chronic pain patients with either chronic back pain (CBP) or osteoarthritis

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