At present, the diagnosis of multiple sclerosis (MS) relies heavily on the use of MRI, which can demonstrate disease dissemination in space and time [1][2][3][4] . The current 2010 McDonald criteria have enabled earlier diagnosis 5,6 and initiation of disease-modifying treatment, with substantial benefits for disease outcome 7,8 , but they still have imperfect sensitivity and specificity 9,10 . The limited accuracy of the criteria results in challenging cases and misdiagnosis, which are prevalent problems in MS 11,12 . Therefore, more-accurate and pathologically specific MRI criteria are still needed to exclude other disorders that can mimic MS 13,14 .The MRI-detectable central vein inside white matter lesions has recently been proposed as a biomarker of inflammatory demyelination and, thus, may aid the diagnosis of MS 15 . The 'central vein sign' (CVS) has been investigated in various neurological conditions by several groups, and evidence has accumulated that the CVS may have the ability to accurately differentiate MS from its mimics [15][16][17][18][19][20][21] . As a consequence, recent guidelines from the Magnetic Resonance Imaging in MS (MAGNIMS) group 1,4 and the Consortium of MS Centers (CMSC) task force 22 have acknowledged the potential of the CVS and its dedicated MRI acquisitions for the differential diagnosis of MS, while calling for further research before considering a possible modification of the diagnostic criteria. However, the lack of standardization for the definition and imaging of the CVS, as well as a dearth of large-scale prospective studies evaluating the CVS for MS diagnosis, are currently preventing the clinical validation of this potential biomarker 1,23 .This Consensus Statement aims to provide recommendations for the definition, standardization and clinical evaluation of the CVS in the diagnosis of MS. These statements are based on a thorough review of the existing literature on the CVS and the consensus opinion of the members of the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative. E X P E RT C O N S E N S U S D O C U M E N T on behalf of the NAIMS CooperativeAbstract | Over the past few years, MRI has become an indispensable tool for diagnosing multiple sclerosis (MS). However, the current MRI criteria for MS diagnosis have imperfect sensitivity and specificity. The central vein sign (CVS) has recently been proposed as a novel MRI biomarker to improve the accuracy and speed of MS diagnosis. Evidence indicates that the presence of the CVS in individual lesions can accurately differentiate MS from other diseases that mimic this condition. However, the predictive value of the CVS for the development of clinical MS in patients with suspected demyelinating disease is still unknown. Moreover, the lack of standardization for the definition and imaging of the CVS currently limits its clinical implementation and validation. On the basis of a thorough review of the existing literature on the CVS and the consensus opinion of the members of the North American Imaging in Mult...

Summary Objective The periaqueductal gray matter (PAG), a known modulator of somatic pain transmission, shows evidence of interictal functional and structural abnormalities in migraineurs, which may contribute to hyperexcitability along spinal and trigeminal nociceptive pathways, and lead to the migraine attack. The aim of this study was to examine functional connectivity of the PAG in migraine. Methods Using resting-state functional MRI, we compared functional connectivity between PAG and a subset of brain areas involved in nociceptive/somatosensory processing and pain modulation in 17 subjects with migraine, during a pain free state, versus 17 gender- and age-matched controls. We also assessed the relation between intrinsic resting-state correlations within PAG networks and the average monthly frequency of migraine attacks, as well as allodynia. Results Our findings show stronger connectivity between the PAG and several brain areas within nociceptive and somatosensory processing pathways in migraineurs versus controls. In addition, as the monthly frequency of migraine attacks worsens, the strength of the connectivity in some areas within these pathways increases while a significant decrease in functional resting-state connectivity between the PAG and brain regions with a predominant role in pain modulation (prefrontal cortex, anterior cingulate, amygdala) can be evidenced. Finally, migraineurs with a history of allodynia exhibit significantly reduced connectivity between PAG, prefrontal regions and anterior cingulate compared to migraineurs without allodynia. Conclusions These data reveal interictal dysfunctional dynamics within pain pathways in migraine manifested as an impairment of the descending pain modulatory, likely leading to loss of pain inhibition, and hyperexcitability primarily in nociceptive areas.