Laura Marcuccio

Executive resting-state network connectivity in migraine without aura.

Background: Converging neuropsychological evidence suggests that in migraine executive functions (EF) may be affected during interictal periods. Objective: To evaluate the functional connectivity of the fronto-parietal networks (FPN) known to be associated with EF, in migraine without aura (MwoA) patients, in the interictal period, in comparison to healthy controls (HC). Methods: Using resting-state functional MRI (RS-fMRI), we compared functional connectivity within the FPN in 14 patients with MwoA versus 14 sex- and age-matched HC, and assessed the correlation between functional connectivity within FPN, clinical features of MwoA patients, and EF. We used voxel-based morphometry to assess whether between-group differences in functional connectivity were dependent on structural differences. Results: Neuropsychological data revealed no significant executive dysfunction in MwoA patients. RS-fMRI showed that MwoA patients, compared to HC, had significant functional connectivity reduction within the right FPN and specifically in the middle frontal gyrus (MFG) and the dorsal anterior cingulate cortex. In addition, we found that MFG reduced connectivity was negatively correlated with the pain intensity of migraine attacks. There were no structural differences between the two groups. Conclusions: Our data suggest that, even in the absence of clinically evident EF deficits, MwoA is associated with reduced FPN functional connectivity. This study provides further insights into the complex scenario of migraine mechanisms.

Pain processing in patients with migraine: an event-related fMRI study during trigeminal nociceptive stimulation

We explored the functional pattern of the pain-processing network in patients with migraine, in the interictal periods, during trigeminal noxious stimulation. Contact heat evoked potential stimulation induced thermal pain and functional magnetic resonance imaging were used to measure whole-brain activation in 16 patients with episodic migraine without aura and 16 age- and gender-matched healthy controls in response to a severe (53°C) noxious, a moderate (51°C) noxious, and a control (41°C) stimulus applied to the maxillary skin. When comparing the fMRI activation over the entire brain, patients with migraine, with respect to healthy controls, showed a significantly greater activation in the perigenual part of anterior cingulate cortex at 51°C and less activation in the bilateral secondary somatosensory cortex at 53°C. A group-by-stimulus interaction analysis revealed a region in the pons showing a divergent response in patients and healthy controls. Correlation analyses demonstrated that the pons activation correlated with higher headache-related disability in patients. Our findings demonstrate increased antinociceptive activity in patients with migraine, which may represent a compensatory reorganization to modulate pain perception at the same intensity of healthy controls.

Functional interictal changes of pain processing in migraine with ictal cutaneous allodynia

Objective A prospective clinical imaging study has been conducted to investigate pain processing functional pathways during trigeminal heat stimulation (THS) in patients with migraine without aura experiencing ictal cutaneous allodynia (CA) (MwoA CA+). Methods Using whole-brain BOLD-fMRI, functional response to THS at three different intensities (41°, 51° and 53℃) was investigated interictally in 20 adult MwoA CA+ patients compared with 20 MwoA patients without ictal CA (MwoA CA−) and 20 healthy controls (HCs). Secondary analyses evaluated associations between BOLD signal change and clinical features of migraine. Results During moderate-noxious THS (51℃), we observed a significantly greater activation in (a) the anterior cingulate cortex in MwoA CA+ patients compared to HCs and (b) the middle frontal gyrus in MwoA CA+ patients compared to both MwoA CA− patients and HCs. Furthermore, during high-noxious THS (53℃) a significantly decreased activation in the secondary somatosensory cortices was observed in (a) MwoA CA− patients compared to both MwoA CA+ patients and HCs and (b) MwoA CA+ patients compared to HCs. CA severity was positively correlated with the secondary somatosensory cortices activation. Conclusions Our findings suggest that CA may be subtended by both a dysfunctional analgesic compensatory mechanism and an abnormal internal representation of pain in migraine patients.

Functional Changes of the Perigenual Part of the Anterior Cingulate Cortex after External Trigeminal Neurostimulation in Migraine Patients

Objective To explore the functional reorganization of the pain processing network during trigeminal heat stimulation (THS) after 60 days of external trigeminal neurostimulation (eTNS) in migraine without aura (MwoA) patients between attacks. Methods Using whole-brain BOLD-fMRI, functional response to THS at two different intensities (41 and 51°C) was investigated interictally in 16 adults MwoA patients before and after eTNS with the Cefaly® device. We calculated the percentage of patients having at least a 50% reduction of monthly migraine attacks and migraine days between baseline and the last month of eTNS. Secondary analyses evaluated associations between BOLD signal changes and clinical features of migraine. Results Before eTNS treatment, there was no difference in BOLD response between MwoA patients and healthy controls (HC) during low-innocuous THS at 41°C, whereas the perigenual part of the right anterior cingulate cortex (ACC) revealed a greater BOLD response to noxious THS at 51°C in MwoA patients when compared to HC. The same area demonstrated a significant reduced BOLD response induced by the noxious THS in MwoA patients after eTNS (p = 0.008). Correlation analyses showed a significant positive correlation between ACC BOLD response to noxious THS before eTNS treatment and the decrease of ACC BOLD response to noxious THS after eTNS. Moreover, a significant negative correlation in the migraine group after eTNS treatment between ACC functional activity changes and both the perceived pain ratings during noxious THS and pre-treatment migraine attack frequency has been found. Conclusion Our findings suggest that eTNS treatment with the Cefaly® device induces a functional antinociceptive modulation in the ACC that is involved in the mechanisms underlying its preventive anti-migraine efficacy. Nevertheless, further observations to confirm whether the observed fMRI effects of eTNS are both related to clinical improvement and specific to antinociceptive modulation in migraine patients are mandatory.

O021. Abnormal connectivity within executive resting-state network in migraine with aura

Background Despite the fact that the clinical features of migraine are well described, the relationship between migraine and cognitive performance is still poorly understood. Indeed, some authors have reported the presence of cognitive deficits in patients with migraine without aura (MwoA) and with aura (MwA) whereas others have not confirmed these findings. Although neuropsychological studies in migraine are not conclusive, the most likely pattern of neuropsychological impairment would relate to the cognitive domain of executive functions (EF) [1]. Recent imaging studies have shown a significant functional connectivity decrease within the fronto-parietal networks (FPN), known to be associated with EF, in patients with MwoA in absence of significant executive dysfunction [2]. Objective To further explore FPN functional connectivity in patients with MwA and patients with MwoA, in the interictal period. Methods Using resting-state functional magnetic resonance imaging (RS-fMRI), we compared functional connectivity within the FPN in 20 patients with MwA, versus 20 sex- and agematched healthy controls (HC). To examine the specificity of any observed differences in FPN functional connectivity between patients and HC, we further studied 20 age- and sex-matched patients with MwoA. Furthermore, we assessed the correlation between functional connectivity within FPN and EF in both migraine groups. Finally, we used voxel-based morphometry to assess whether between-group differences in functional connectivity were dependent on structural differences. Results Neuropsychological data revealed no significant executive dysfunction in both migraine groups compared to HC. RS-fMRI showed that both MwA and MwoA patients, compared to HC, had a significant functional connectivity decrease within the right FPN and specifically in the middle frontal gyrus and the dorsal anterior cingulate cortex. There were no structural differences between the three groups. Conclusions Our data demonstrate that, even in the absence of clinically evident EF deficits, MwA and MwoA are associated with reduced FPN functional connectivity. We suggest that disrupted FPN functional connectivity might be only a part of a complex cascade that terminates in a migraine attack. In this context, FPN abnormalities may be the neuronal substrate on which biological, genetic and environmental factors could induce, and in turn correlate with, migraine attacks mostly characterized by high pain intensity in patients with MwoA and aura phenomenon in patients with MwA. In other terms, observed FPN connectivity changes may represent a migraine biomarker, probably related to well-known maladaptive stress response in migraine patients. Written informed consent to publish was obtained from the patient(s).

Hemiparkinsonism and hemiatrophy syndrome: a rare observation.

Hemiparkinsonism with hemiatrophy syndrome is defined by the occurrence of a body hemiatrophy with features of an early onset, slowly progressive, asymmetric parkinsonism more prominent on the side of the hemiatrophy. The underlying pathogenesis is not well understood but perinatal cerebral insults seem to play a crucial role. We describe the case of a 52-year-old woman who presented with a two year history of slowness and stiffness of left arm and leg with dystonic posturing of the ipsilateral hand. When examined, she had a left body hemiatrophy which was present since early childhood. Clinical and imaging findings supported the diagnosis of hemiparkinsonism with hemiatrophy syndrome with a good response to dopamine agonist therapy. This case report further characterizes this heterogeneous form of parkinsonism which deserves attention for clinical management and prognostic evaluation.

Migraine Does Not Affect Pain Intensity Perception: A Cross-Sectional Study

Objective To explore perceived pain intensity (PPI) in three drug-naïve patient groups characterized by homogeneous migraine phenotypes-migraine without aura without cutaneous allodynia (MwoA CA-), MwoA with ictal CA (MwoA CA+), and migraine with aura without cutaneous allodynia (MwA CA-)-compared with age- and sex-matched healthy controls (HCs). Methods Using trigeminal heat stimulation (THS) at three different predefined intensities (41 °C, 51 °C, and 53 °C) performed by the contact heat-evoked potential stimulator (CHEPS), PPI was investigated in 34 patients with MwoA CA-, 30 patients with MwoA CA+, and 30 patients with MwA CA- compared with 30 age- and sex-matched HCs. The patients had never taken migraine-preventive drugs, and they were investigated during an interictal period to avoid confounds associated with migraine attack. Secondary analyses evaluated associations between PPI and clinical features of migraine in patients. Results No significant differences were observed between the four groups for each experimentally induced stimulus. Moreover, no significant correlations were found between clinical variables and the PPI of the THS at any level of experimental stimulus. Conclusions Despite the converging evidence of pain threshold abnormalities in migraine patients, our findings suggest that migraine patients did not exhibit differences in the PPI of THS when compared with HCs, independent of phenotype and migraine severity, as well as somatic, psychiatric, or pharmacological interferences. This may depend on both the nature of the pain stimulus experienced and the involvement of selective regions or specific pain processing pathways.

Prospective memory is dysfunctional in migraine without aura

Introduction Prospective memory is the ability to carry out a delayed intended action, so to maintain and retrieve future plans, goals and activities. Deficits of prospective memory negatively impact on patients and caregivers’ everyday living and determine poor adherence to treatment. Since frontal regions are involved in both event- and time-based prospective memory tasks and are impaired in migraine without aura, defects of prospective memory might occur in migraine without aura patients; until now this issue has not been investigated. The aim of the current study was to explore time- versus event-based prospective memory in migraine without aura. Patients and methods Ninty-one consecutive migraine without aura patients and 84 healthy subjects were enrolled in the study. They underwent a standardized measure of prospective memory evaluating both time-based and event-based prospective memory, and the Montreal Cognitive Assessment assessing global cognitive status. Moreover, all participants completed the Beck Depression Inventory-II and a self-administered version of the Apathy Evaluation Scale, to assess severity of depressive symptoms and apathy, respectively. Results Migraine without aura and healthy subjects did not differ on demographic aspects (i.e. age, education and gender). However, individuals with migraine without aura demonstrated impaired prospective memory performance compared to healthy subjects, with a greater impairment demonstrated for the time-based tasks. Within the migraine without aura group, no significant association was found between prospective memory performance and clinical scores, apathy, and depression. Conclusions Individuals with migraine without aura experience particular difficulty executing a future intention; therefore, migraine without aura is associated with dysfunction of prospective memory.

P018. No evidence of microstructural changes in patients with vestibular migraine: a diffusion tensor tract based spatial statistic (TBSS) study

Background Vestibular migraine (VM) has been increasingly recognized as a possible cause of episodic vertigo [1], but its pathophysiology is still unclear. In our previous fMRI study, we had observed a significantly increased thalamic activation in patients with vestibular migraine (VM) during vestibular stimulation in comparison with patients with migraine without aura (MwoA) and healthy controls (HC) [2]. Recently, a voxel based morphometry (VBM) study has shown gray matter volume reduction in brain areas involved in pain and vestibular processing [3]. However, no studies have yet investigated white matter (WM) microstructural abnormalities in patients with VM. Objective To investigate whole-brain and thalamic WM microstructural changes in patients with VM, compared with patients with MwoA and HC. Methods By using magnetic resonance imaging and diffusion tensor imaging (DTI) with tract-based spatial statistic (TBSS) analysis [4], we analyzed WM integrity in twenty patients with VM, compared to twenty patients with MwoA and twenty HC. We performed a TBSS analysis generating fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) and axial diffusivity (AD) maps. TBSS was run with FA maps to create the “skeleton”, which represents the center of all fiber bundles in common to all subjects. The resulting statistical maps were thresholded at p < 0.05 corrected for multiple comparisons at a cluster level. Besides whole brain analyses, a region of interest (ROI) analysis was also performed to correlate the TBSS results with both thalamic standard anatomic ROI data and functional regions that were based on the results of our previous fMRI study. Results Between-groups analyses did not reveal statistically significant differences in both whole-brain and bilateral thalamic ROI FA, MD, RD and AD values between patients with VM compared with patients with MwoA and HC (p < 0.05 corrected). Conclusions Recent studies have demonstrated that the thalamus may play a major role in an abnormal information processing during ictal and interictal migraineous periods. Our previous fMRI study has clearly demonstrated an abnormal thalamic activation during vestibular processing in patients with VM. However, this functional phenomenon seems not be correlated to any structural connectivity changes since both whole-brain and thalamic ROI DTI analyses have not demonstrated significant differences between VM, MwoA and HC. Our preliminary data may support the hypothesis that thalamic functional changes may not be linked to, or alternatively, may precede structural abnormalities in patients with VM. Written informed consent to publish was obtained from the patient(s).

P017. Ictal cutaneous allodynia does not affect pain perception in patients with migraine: a trigeminal heat stimulation study during interictal period

Background Migraine is a disabling neurological condition characterized by headache attacks, hypersensitivities to visual, auditory, olfactory and somatosensory stimuli, nausea and vomiting. Peripheral and central sensitization of trigeminovascular neurons seem to play a critical role in different aspects of migraine pathophysiology [1]. In the last years, several studies investigated pain thresholds in patients with migraine during both attacks and interictal periods. However, pain perception in patients with migraine has been poorly explored. Objective To investigate perception intensity of trigeminal heat stimulation (THS) [2] in patients with migraine without (MwoA CA-) and with allodynia (MwoA CA+) compared to healthy controls (HC) and correlation with clinical parameters of migraine severity. Methods We enrolled 80 patients with migraine (40 patients with MwoA CA- and 40 patients with MwoA CA+) and 60 HC. THS was performed using the contact heat evoked potential stimulator (CHEPS) at three different intensities: a low-innocuous stimulus at 41°C and two painful heat stimuli at 51° and 53°C (to provide a moderate-noxious and a high-noxious stimulus). Subjects had to verbally rate the intensity perception of the experimental stimulus by means of a numerical rating scale (NRS) ranging from 0( “no pain” )t o 10 (“worst pain imaginable”). Results NRS of pain perception was not significantly different between patients with MwoA (as a group) and HC at any level of experimental stimuli. The absence of significant differences in pain perception was also found between patient groups defined as patients with MwoA CA- and with MwoA CA+ compared to HC, at any level of experimental stimuli. Conclusions