Publications by authors named "Cherubino DI Lorenzo"

74 Publications

Pathophysiological Bases of Comorbidity in Migraine.

Front Hum Neurosci 2021 20;15:640574. Epub 2021 Apr 20.

Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino, Latina, Italy.

Despite that it is commonly accepted that migraine is a disorder of the nervous system with a prominent genetic basis, it is comorbid with a plethora of medical conditions. Several studies have found bidirectional comorbidity between migraine and different disorders including neurological, psychiatric, cardio- and cerebrovascular, gastrointestinal, metaboloendocrine, and immunological conditions. Each of these has its own genetic load and shares some common characteristics with migraine. The bidirectional mechanisms that are likely to underlie this extensive comorbidity between migraine and other diseases are manifold. Comorbid pathologies can induce and promote thalamocortical network dysexcitability, multi-organ transient or persistent pro-inflammatory state, and disproportionate energetic needs in a variable combination, which in turn may be causative mechanisms of the activation of an ample defensive system with includes the trigeminovascular system in conjunction with the neuroendocrine hypothalamic system. This strategy is designed to maintain brain homeostasis by regulating homeostatic needs, such as normal subcortico-cortical excitability, energy balance, osmoregulation, and emotional response. In this light, the treatment of migraine should always involves a multidisciplinary approach, aimed at identifying and, if necessary, eliminating possible risk and comorbidity factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnhum.2021.640574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093831PMC
April 2021

Visual Evoked Potential Responses after Photostress in Migraine Patients and Their Correlations with Clinical Features.

J Clin Med 2021 Mar 2;10(5). Epub 2021 Mar 2.

IRCCS-Fondazione Bietti, Via Livenza 3, 00198 Rome, Italy.

In the past few years, researchers have detected subtle macular vision abnormalities using different psychophysical experimental tasks in patients with migraine. Recording of visual evoked potential (VEP) after photostress (PS) represents an objective way to verify the integrity of the dynamic properties of macular performance after exposure to intense light. VEPs were recorded before and after PS in 51 patients with migraine (19 with aura (MA) and 22 without aura (MO) between attacks, and 10 recorded during an attack (MI)) and 14 healthy volunteers. All study participants were exposed to 30 s of PS through the use of a 200-watt bulb lamp. The P100 implicit time and N75-P100 amplitude of the baseline VEP were compared with those collected every 20 s up to 200 s after PS. VEP parameters recorded at baseline did not differ between groups. In all groups, the VEP recordings exhibited a significant increase in implicit times and a reduction in amplitude at 20 s after the PS. In migraine, the percentage decrease in amplitudes observed at 20 s after photostress was significantly lower than in healthy volunteers, in both MO and MA patients, but not in MI patients. When data for MO and MA patients were combined, the percentage of amplitude change at 20 s was negatively correlated with the number of days that had elapsed since the last migraine attack, and positive correlated with attack frequency. We showed dynamic changes of recovery of VEP after PS depending on the migraine cycle. This finding, in conjunction with those previously attained with other neuromodulatory interventions using VEPs, leads us to argue that migraine-disease-related dysrhythmic thalamocortical activity precludes amplitude suppression by PS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10050982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957878PMC
March 2021

One Hour-Post-load Plasma Glucose ≥155 mg/dl in Healthy Glucose Normotolerant Subjects Is Associated With Subcortical Brain MRI Alterations and Impaired Cognition: A Pilot Study.

Front Aging Neurosci 2021 4;13:608736. Epub 2021 Feb 4.

Geriatrics Division, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.

Glucose alterations are associated with impaired cognition. The 1-h-post-load plasma glucose ≥155 mg/dl in non-diabetic subjects confers an increased risk of cardiovascular events and diabetes. This pilot study aimed to investigate whether the 1-h-post-load plasma glucose ≥155 mg/dl negatively affects the subcortical regions of the brain and the cognitive functions. We enrolled 32 non-diabetic subjects. Patients were divided into two groups based on 1-h- post-load plasma glucose value > or < 155 mg/dl: normal glucose tolerance (NGT) 1-h-high and NGT 1-h-low subjects. All subjects underwent 3 Tesla MRI and standard neuropsychological tests. NGT 1-h-high subjects showed significantly lower values of both right (4.9 ± 0.9 vs. 5.1 ± 0.9 ml) and left (4.8 ± 1.1 vs. 5.1 ± 1.1 ml) hippocampal hemisphere volume, while right hemisphere hippocampal diffusivity was lower in the NGT 1-h-high group (10.0 ± 0.6 vs. 10.6 ± 0.5 10 mms). NGT 1-h-high subjects also showed a poorer memory performance. In particular, for both Rey Auditory Verbal Learning Task (RAVLT)-immediate-recall and Free and Cued Selective Reminding Test (FCSRT)-delayed total recall, we found lower cognitive test scores in the NGT-1 h-high group (26.5 ± 6.3 and 10.4 ± 0.3, respectively). One-hour-post-load hyperglycemia is associated with morpho-functional subcortical brain alterations and poor memory performance tests.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnagi.2021.608736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891177PMC
February 2021

An artificial neural network approach to detect presence and severity of Parkinson's disease via gait parameters.

PLoS One 2021 19;16(2):e0244396. Epub 2021 Feb 19.

Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina, Italy.

Introduction: Gait deficits are debilitating in people with Parkinson's disease (PwPD), which inevitably deteriorate over time. Gait analysis is a valuable method to assess disease-specific gait patterns and their relationship with the clinical features and progression of the disease.

Objectives: Our study aimed to i) develop an automated diagnostic algorithm based on machine-learning techniques (artificial neural networks [ANNs]) to classify the gait deficits of PwPD according to disease progression in the Hoehn and Yahr (H-Y) staging system, and ii) identify a minimum set of gait classifiers.

Methods: We evaluated 76 PwPD (H-Y stage 1-4) and 67 healthy controls (HCs) by computerized gait analysis. We computed the time-distance parameters and the ranges of angular motion (RoMs) of the hip, knee, ankle, trunk, and pelvis. Principal component analysis was used to define a subset of features including all gait variables. An ANN approach was used to identify gait deficits according to the H-Y stage.

Results: We identified a combination of a small number of features that distinguished PwPDs from HCs (one combination of two features: knee and trunk rotation RoMs) and identified the gait patterns between different H-Y stages (two combinations of four features: walking speed and hip, knee, and ankle RoMs; walking speed and hip, knee, and trunk rotation RoMs).

Conclusion: The ANN approach enabled automated diagnosis of gait deficits in several symptomatic stages of Parkinson's disease. These results will inspire future studies to test the utility of gait classifiers for the evaluation of treatments that could modify disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244396PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894951PMC
February 2021

Genetics Influences Drug Consumption in Medication Overuse Headache, Not in Migraine: Evidence From Wolframin His611Arg Polymorphism Analysis.

Front Neurol 2020 22;11:599517. Epub 2021 Jan 22.

Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino, Latina, Italy.

The Wolframin His611Arg polymorphism can influence drug consumption in psychiatric patients with impulsive addictive behavior. This cross-sectional study aims to assess the prevalence of the Wolframin His611Arg polymorphism in MOH, a secondary headache belonging to the spectrum of addictive disorders, episodic migraine (EM), and healthy subjects (HS), and its influence on drug consumption. One-hundred and seventy-two EM, 107 MOH, and 83 HS were enrolled and genotyped for the Wolframin His611Arg polymorphism. Subjects were classified as homozygous for allele His (H/H subjects), homozygous for allele Arg (R/R subjects), and heterozygous (H/R subjects), regrouped as R/R and carriers of allele H (non-R/R), and matched for clinical data. There were no differences in allelic distributions between the three groups ( = 0.19). Drug consumption and other clinical characteristics were not influenced by the Wolframin His611Arg polymorphism ( = 0.42; β = 0.04) in the EM group. Among the MOH population, R/R subjects consumed more analgesics ( < 0.0001; β = -0.38), particularly combination drugs ( = 0.0001; = 2.32). The Wolframin His611Arg polymorphism has a similar prevalence between the MOH, EM, and HS groups. The presence of the R/R genotype does not influence symptomatic drug consumption in EM, whereas it determines an increased use of symptomatic drugs in the MOH group, in particular combination drugs (i.e., drugs containing psychoactive compounds). Our findings are consistent with the hypothesis that the Wolframin His611Arg polymorphism plays its effect only in the MOH population, influencing the impulsivity control underlying addictive behavior.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2020.599517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862332PMC
January 2021

Patients with chronic migraine without history of medication overuse are characterized by a peculiar white matter fiber bundle profile.

J Headache Pain 2020 Jul 18;21(1):92. Epub 2020 Jul 18.

Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino, Latina, Italy.

Background: We investigated intracerebral fiber bundles using a tract-based spatial statistics (TBSS) analysis of diffusion tensor imaging (DTI) data to verify microstructural integrity in patients with episodic (MO) and chronic migraine (CM).

Methods: We performed DTI in 19 patients with MO within interictal periods, 18 patients with CM without any history of drug abuse, and 18 healthy controls (HCs) using a 3 T magnetic resonance imaging scanner. We calculated diffusion metrics, including fractional anisotropy (FA), axial diffusion (AD), radial diffusion (RD), and mean diffusion (MD).

Results: TBSS revealed no significant differences in the FA, MD, RD, and AD maps between the MO and HC groups. In comparison to the HC group, the CM group exhibited widespread increased RD (bilateral superior [SCR] and posterior corona radiata [PCR], bilateral genu of the corpus callosum [CC], bilateral posterior limb of internal capsule [IC], bilateral superior longitudinal fasciculus [LF]) and MD values (tracts of the right SCR and PCR, right superior LF, and right splenium of the CC). In comparison to the MO group, the CM group showed decreased FA (bilateral SCR and PCR, bilateral body of CC, right superior LF, right forceps minor) and increased MD values (bilateral SCR and right PCR, right body of CC, right superior LF, right splenium of CC, and right posterior limb of IC).

Conclusion: Our results suggest that chronic migraine can be associated with the widespread disruption of normal white matter integrity in the brain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s10194-020-01159-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368770PMC
July 2020

Short-latency afferent inhibition and somato-sensory evoked potentials during the migraine cycle: surrogate markers of a cycling cholinergic thalamo-cortical drive?

J Headache Pain 2020 Apr 16;21(1):34. Epub 2020 Apr 16.

Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino, Corso della Repubblica 79, 04100, Latina, Italy.

Background: Short-latency afferent inhibition (SAI) consists of motor cortex inhibition induced by sensory afferents and depends on the excitatory effect of cholinergic thalamocortical projections on inhibitory GABAergic cortical networks. Given the electrophysiological evidence for thalamo-cortical dysrhythmia in migraine, we studied SAI in migraineurs during and between attacks and searched for correlations with somatosensory habituation, thalamocortical activation, and clinical features.

Methods: SAI was obtained by conditioning the transcranial magnetic stimulation-induced motor evoked potential (MEP) with an electric stimulus on the median nerve at the wrist with random stimulus intervals corresponding to the latency of individual somatosensory evoked potentials (SSEP) N20 plus 2, 4, 6, or 8 ms. We recruited 30 migraine without aura patients, 16 between (MO), 14 during an attack (MI), and 16 healthy volunteers (HV). We calculated the slope of the linear regression between the unconditioned MEP amplitude and the 4-conditioned MEPs as a measure of SAI. We also measured SSEP amplitude habituation, and high-frequency oscillations (HFO) as an index of thalamo-cortical activation.

Results: Compared to HV, SAI, SSEP habituation and early SSEP HFOs were significantly reduced in MO patients between attacks, but enhanced during an attack. There was a positive correlation between degree of SAI and amplitude of early HFOs in HV, but not in MO or MI.

Conclusions: The migraine cycle-dependent variations of SAI and SSEP HFOs are further evidence that facilitatory thalamocortical activation (of GABAergic networks in the motor cortex for SAI), likely to be cholinergic, is reduced in migraine between attacks, but increased ictally.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s10194-020-01104-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164277PMC
April 2020

The function of the lateral inhibitory mechanisms in the somatosensory cortex is normal in patients with chronic migraine.

Clin Neurophysiol 2020 04 3;131(4):880-886. Epub 2020 Feb 3.

Sapienza University of Rome Polo Pontino, Department of Medico-Surgical Sciences and Biotechnologies, Latina, Italy; IRCCS Neuromed, Pozzilli, IS, Italy.

Objective: To study lateral inhibition and habituation/sensitization in the somatosensory cortex of patients with chronic migraine (CM) and to identify correlations with clinical migraine features.

Methods: Sixteen patients with CM without medication overuse, and 17 healthy volunteers (HVs) received somatosensory evoked potentials (SSEPs) elicited by separate electrical stimulation of the right median (M) and ulnar (U) nerves at the wrist and by simultaneous nerve stimulation (MU). We measured the N20-P25 amplitudes and calculated the lateral inhibition (LI) percentage using the formula {100-[MU/(M + U) * 100]}. We also calculated sensitization (SSEP amplitude during block 1) and delayed habituation to M-nerve stimulation.

Results: The percentage of LI did not differ between the groups (40.2% in HV, 47.4% in CM, p = 0.276) and was negatively correlated with the monthly headache-day number (r = -0.532, p = 0.034). Patients showed a generalized increase in SSEP amplitudes compared to HVs and habituated normally.

Conclusions: We showed a pattern of somatosensory response in CM similar to that observed during attacks of episodic migraine.

Significance: In the transition process between episodic migraine and CM, LI attempts to physiologically counteract the mounting increase in attack frequency, but this is insufficient to allow patients to exit the chronic phase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinph.2020.01.009DOI Listing
April 2020

Increased neural connectivity between the hypothalamus and cortical resting-state functional networks in chronic migraine.

J Neurol 2020 Jan 12;267(1):185-191. Epub 2019 Oct 12.

Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino, Latina, Italy.

Objective: The findings of resting-state functional MRI studies have suggested that abnormal functional integration between interconnected cortical networks characterises the brain of patients with migraine. The aim of this study was to investigate the functional connectivity between the hypothalamus, brainstem, considered as the migraine generator, and the following areas/networks that are reportedly involved in the pathophysiology of migraine: default mode network (DMN), executive control network, dorsal attention system, and primary and dorsoventral visual networks.

Methods: Twenty patients with chronic migraine (CM) without medication overuse and 20 healthy controls (HCs) were prospectively recruited. All study participants underwent 3-T MRI scans using a 7.5-min resting-state protocol. Using a seed-based approach, we performed a ROI-to-ROI analysis selecting the hypothalamus as the seed.

Results: Compared to HCs, patients with CM showed significantly increased neural connectivity between the hypothalamus and brain areas belonging to the DMN and dorsal visual network. We did not detect any connectivity abnormalities between the hypothalamus and the brainstem. The correlation analysis showed that the severity of the migraine headache was positively correlated with the connectivity strength of the hypothalamus and negatively with the connectivity strength of the medial prefrontal cortex, which belongs to the DMN.

Conclusion: These data provide evidence for hypothalamic involvement in large-scale reorganisation at the functional-network level in CM and in proportion with the perceived severity of the migraine pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-019-09571-yDOI Listing
January 2020

Prediction of Responsiveness of Gait Variables to Rehabilitation Training in Parkinson's Disease.

Front Neurol 2019 2;10:826. Epub 2019 Aug 2.

Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.

Gait disorders represent one of the most disabling features of Parkinson's disease, which may benefit from rehabilitation. No consistent evidence exists about which gait biomechanical factors can be modified by rehabilitation and which clinical characteristic can predict rehabilitation-induced improvements. The aims of the study were as follows: (i) to recognize the gait parameters modifiable by a short-term rehabilitation program; (ii) to evaluate the gait parameters that can normalize after rehabilitation; and (iii) to identify clinical variables predicting improvements in gait function after rehabilitation. Thirty-six patients affected by idiopathic Parkinson's disease in Hoehn-Yahr stage 1-3 and 22 healthy controls were included in the study. Both clinical and instrumental (gait analysis) evaluations were performed before and after a 10-weeks rehabilitation treatment. Time-distance parameters, lower limb joint, and trunk kinematics were measured. At baseline evaluation with matched speed, almost all gait parameters were significantly different between patients and healthy controls. After the 10-weeks rehabilitation, most gait parameters improved, and spatial asymmetry and trunk rotation normalized. Multiple linear regression of gender combined with Unified Parkinson's Disease Rating Scale-III predicted both ΔSpeed and ΔStep length of both sides; gender combined with Unified Parkinson's Disease Rating Scale-II predicted ΔCadence; age combined with Hoehn-Yahr score and disease duration predicted Δtrunk rotation range of motion. Impaired gait parameters are susceptible to improvement by rehabilitation, and younger men with Parkinson's disease who are less severely affected and at early disease stage are more susceptible to improvements in gait function after a 10-weeks rehabilitation program.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2019.00826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688512PMC
August 2019

A Randomized Double-Blind, Cross-Over Trial of very Low-Calorie Diet in Overweight Migraine Patients: A Possible Role for Ketones?

Nutrients 2019 Jul 28;11(8). Epub 2019 Jul 28.

Department of Experimental Medicine, Sapienza University of Rome, 00161 Roma, Italy.

Here we aimed at determining the therapeutic effect of a very low-calorie diet in overweight episodic migraine patients during a weight-loss intervention in which subjects alternated randomly between a very low-calorie ketogenic diet (VLCKD) and a very low-calorie non-ketogenic diet (VLCnKD) each for one month. In a nutritional program, 35 overweight obese migraine sufferers were allocated blindly to 1-month successive VLCKD or VLCnKD in random order (VLCKD-VLCnKD or VLCnKD-VLCD). The primary outcome measure was the reduction of migraine days each month compared to a 1-month pre-diet baseline. Secondary outcome measures were 50% responder rate for migraine days, reduction of monthly migraine attacks, abortive drug intake and body mass index (BMI) change. Only data from the intention-to-treat cohort ( = 35) will be presented. Patients who dropped out ( = 6) were considered as treatment failures. Regarding the primary outcome, during the VLCKD patients experienced -3.73 (95% CI: -5.31, -2.15) migraine days respect to VLCnKD ( < 0.0001). The 50% responder rate for migraine days was 74.28% (26/35 patients) during the VLCKD period, but only 8.57% (3/35 patients) during VLCnKD. Migraine attacks decreased by -3.02 (95% CI: -4.15, -1.88) during VLCKD respect to VLCnKD ( < 0.00001). There were no differences in the change of acute anti-migraine drug consumption ( = 0.112) and BMI ( = 0.354) between the 2 diets. A VLCKD has a preventive effect in overweight episodic migraine patients that appears within 1 month, suggesting that ketogenesis may be a useful therapeutic strategy for migraines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu11081742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722531PMC
July 2019

Availability of Effective Evidence-Based Symptomatic Treatments for Cluster Headache in the EU Countries-A Survey of the European Headache Alliance and European Headache Federation.

J Oral Facial Pain Headache 2020 24;34(1):7–12. Epub 2019 Jul 24.

Aims: To assess the reimbursement options and accessibility of three effective medicines for cluster headache (CH) (subcutaneous sumatriptan, oxygen, and zolmitriptan spray) across the European Union (EU).

Methods: A brief survey investigating the availability of symptomatic treatments for CH was sent by email in January 2017 to at least one headache specialist for every single country in the EU.

Results: The questionnaire was completed by 26 headache specialists (93% of the EU countries, representing 99.75% of the European population) and by 10 CH patients representative of patient organizations. Oxygen was reimbursable for 63% of the CH population. Oxygen device was reimbursable for 50% of the CH EU population. Subcutaneous sumatriptan was reimbursable for 66% and was accessible without restrictions for 45% of the CH EU population. Zolmitriptan spray was reimbursable for 23.7% and accessible without restrictions for 30.9% of the CH EU population.

Conclusion: Only 47% of the EU population had unrestricted access to effective CH treatments, with unacceptable inequalities between eastern countries and the rest of Europe. Headache societies and patient associations should pressure European and national health authorities to improve the availability of effective symptomatic treatments for CH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11607/ofph.2223DOI Listing
January 2020

A ketogenic diet normalizes interictal cortical but not subcortical responsivity in migraineurs.

BMC Neurol 2019 Jun 22;19(1):136. Epub 2019 Jun 22.

Department of Medico-Surgical Sciences and Biotechnologies, "Sapienza" University Rof Rome Polo Pontino, Latina, Italy.

Background: A short ketogenic diet (KD) treatment can prevent migraine attacks and correct excessive cortical response. Here, we aim to prove if the KD-related changes of cortical excitability are primarily due to cerebral cortex activity or are modulated by the brainstem.

Methods: Through the stimulation of the right supraorbital division of the trigeminal nerve, we concurrently interictally recorded the nociceptive blink reflex (nBR) and the pain-related evoked potentials (PREP) in 18 migraineurs patients without aura before and after 1-month on KD, while in metabolic ketosis. nBR and PREP reflect distinct brain structures activation: the brainstem and the cerebral cortex respectively. We estimated nBR R2 component area-under-the-curve as well as PREP amplitude habituation as the slope pof the linear regression between the 1st and the 2nd block of 5 averaged responses.

Results: Following 1-month on KD, the mean number of attacks and headache duration reduced significantly. Moreover, KD significantly normalized the interictal PREP habituation (pre: + 1.8, post: - 9.1, p = 0.012), while nBR deficit of habituation did not change.

Conclusions: The positive clinical effects we observed in a population of migraineurs by a 1-month KD treatment coexists with a normalization at the cortical level, not in the brainstem, of the typical interictal deficit of habituation. These findings suggest that the cerebral cortex may be the primary site of KD-related modulation.

Trial Registration: ClinicalTrials.gov NCT03775252 (retrospectively registered, December 09, 2018).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12883-019-1351-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588932PMC
June 2019

Aberrant interactions of cortical networks in chronic migraine: A resting-state fMRI study.

Neurology 2019 05 3;92(22):e2550-e2558. Epub 2019 May 3.

From the Department of Medico-Surgical Sciences and Biotechnologies (G. Coppola, M.S., F.P.), Sapienza University of Rome Polo Pontino, Latina; Research Unit of Neurophysiology of Vision and Neuroophthalmology (A.D.R., V.P.), IRCCS-Fondazione Bietti; Department of Human Neurosciences (B.P., E.T., V.C., S.T., G. Cartocci, F.C., V.D.P.), Sapienza University of Rome; Don Carlo Gnocchi Onlus Foundation (C.D.L.), Milan, Italy; Headache Research Unit, University Department of Neurology CHR (J.S.), Citadelle Hospital, University of Liège, Belgium; and IRCCS-Neuromed (F.P.), Pozzilli, Italy.

Objective: We investigated resting-state (RS)-fMRI using independent component analysis (ICA) to determine the functional connectivity (FC) between networks in chronic migraine (CM) patients and their correlation with clinical features.

Methods: Twenty CM patients without preventive therapy or acute medication overuse underwent 3T MRI scans and were compared to a group of 20 healthy controls (HC). We used MRI to collect RS data in 3 selected networks, identified using group ICA: the default mode network (DMN), the executive control network (ECN), and the dorsal attention system (DAS).

Results: Compared to HC, CM patients had significantly reduced functional connectivity between the DMN and the ECN. Moreover, in patients, the DAS showed significantly stronger FC with the DMN and weaker FC with the ECN. The higher the severity of headache, the increased the strength of DAS connectivity, and the lower the strength of ECN connectivity.

Conclusion: These results provide evidence for large-scale reorganization of functional cortical networks in chronic migraine. They suggest that the severity of headache is associated with opposite connectivity patterns in frontal executive and dorsal attentional networks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000007577DOI Listing
May 2019

Clinical neurophysiology of migraine with aura.

J Headache Pain 2019 Apr 29;20(1):42. Epub 2019 Apr 29.

Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino, Corso della Repubblica, 79-04100, Latina, Italy.

Background: The purpose of this review is to provide a comprehensive overview of the findings of clinical electrophysiology studies aimed to investigate changes in information processing of migraine with aura patients.

Main Body: Abnormalities in alpha rhythm power and symmetry, the presence of slowing, and increased information flow in a wide range of frequency bands often characterize the spontaneous EEG activity of MA. Higher grand-average cortical response amplitudes, an increased interhemispheric response asymmetry, and lack of amplitude habituation were less consistently demonstrated in response to any kind of sensory stimulation in MA patients. Studies with single-pulse and repetitive transcranial magnetic stimulation (TMS) have reported abnormal cortical responsivity manifesting as greater motor evoked potential (MEP) amplitude, lower threshold for phosphenes production, and paradoxical effects in response to both depressing or enhancing repetitive TMS methodologies. Studies of the trigeminal system in MA are sparse and the few available showed lack of blink reflex habituation and abnormal findings on SFEMG reflecting subclinical, probably inherited, dysfunctions of neuromuscular transmission. The limited studies that were able to investigate patients during the aura revealed suppression of evoked potentials, desynchronization in extrastriate areas and in the temporal lobe, and large variations in direct current potentials with magnetoelectroencephalography. Contrary to what has been observed in the most common forms of migraine, patients with familial hemiplegic migraine show greater habituation in response to visual and trigeminal stimuli, as well as a higher motor threshold and a lower MEP amplitude than healthy subjects.

Conclusion: Since most of the electrophysiological abnormalities mentioned above were more frequently present and had a greater amplitude in migraine with aura than in migraine without aura, neurophysiological techniques have been shown to be of great help in the search for the pathophysiological basis of migraine aura.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s10194-019-0997-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734510PMC
April 2019

Development and validation of the ID-EC - the ITALIAN version of the identify chronic migraine.

J Headache Pain 2019 Feb 13;20(1):15. Epub 2019 Feb 13.

Department of Clinical and Molecular Medicine, Regional Referral Headache Centre, Sant'Andrea Hospital, Sapienza University, Rome, Italy.

Background: Case-finding tools, such as the Identify Chronic Migraine (ID-CM) questionnaire, can improve detection of CM and alleviate its significant societal burden. We aimed to develop and validate the Italian version of the ID-CM (ID-EC) in paper and as a smart app version in a headache clinic-based setting.

Methods: The study investigators translated and adapted to the Italian language the original ID-CM questionnaire (ID-EC) and further implemented it as a smart app. The ID-EC was tested in its paper and electronic version in consecutive patients referring to 9 Italian tertiary headache centers for their first in-person visit. The scoring algorithm of the ID-EC paper version was applied by the study investigators (case-finding) and by patients (self-diagnosis), while the smart app provided to patients automatically the diagnosis. Diagnostic accuracy of the ID-EC was assessed by matching the questionnaire results with the interview-based diagnoses performed by the headache specialists during the visit according to the criteria of International Classification of Headache Disorders, III edition, beta version.

Results: We enrolled 531 patients in the test of the paper version of ID-EC and 427 in the validation study of the smart app. According to the clinical diagnosis 209 patients had CM in the paper version study and 202 had CM in the smart app study. 79.5% of patients returned valid paper questionnaires, while 100% of patients returned valid and complete smart app questionnaires. The paper questionnaire had a 81.5% sensitivity and a 81.1% specificity for case-finding and a 30.7% sensitivity and 90.7% specificity for self-diagnosis, while the smart app had a 64.9% sensitivity and 90.2% specificity.

Conclusions: Our data suggest that the ID-EC, developed and validated in tertiary headache centers, is a valid case-finding tool for CM, with sensitivity and specificity values above 80% in paper form, while the ID-EC smart app is more useful to exclude CM diagnosis in case of a negative result. Further studies are warranted to assess the diagnostic accuracy of the ID-EC in general practice and population-based settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s10194-019-0966-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734365PMC
February 2019

Withdrawal from acute medication normalises short-term cortical synaptic potentiation in medication overuse headache.

Neurol Sci 2019 May 1;40(5):963-969. Epub 2019 Feb 1.

Department of Medico-Surgical Sciences and Biotechnologies, "Sapienza" University of Rome Polo Pontino, Corso della Repubblica 79, 04100, Latina, Italy.

Objectives: To study the effects of a standard acute medication withdrawal program on short-term cortical plasticity mechanisms in patients with medication overuse headache (MOH).

Methods: Thirteen patients with MOH and 16 healthy volunteers underwent repetitive transcranial magnetic stimulation (rTMS) over the left motor cortex; in patients with MOH, recordings were performed before and after a 3-week medication withdrawal program. Ten trains of 10 stimuli each (120% resting motor threshold) were delivered at 1 Hz or 5 Hz in two separate sessions in a randomised order. Motor evoked potential (MEP) amplitudes were measured from the right first dorsal interosseous muscle and the slope of the linear regression line from the first to the tenth stimuli was calculated for each participant.

Results: All subjects exhibited MEP amplitude inhibition in response to 1 Hz rTMS. Alternatively, the 5-Hz trains of rTMS inhibited rather than potentiated MEP amplitudes in patients with MOH. The physiological potentiating effect of 5 Hz rTMS on MEP amplitudes was restored after drug withdrawal and in proportion with the percentage reduction in monthly headache days in patients with MOH.

Conclusions: The results suggest that acute medication withdrawal normalises brain responses in patients with MOH. Clinical improvements after medication withdrawal may reflect the reversal of neurophysiological dysfunction. Accordingly, medication withdrawal should be offered to patients with MOH as early as possible in order to prevent the development of more pronounced alterations in brain plasticity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-019-03735-4DOI Listing
May 2019

SNAP25 Gene Polymorphisms Protect Against Parkinson's Disease and Modulate Disease Severity in Patients.

Mol Neurobiol 2019 Jun 17;56(6):4455-4463. Epub 2018 Oct 17.

IRCCS Fondazione Don Carlo Gnocchi, Milano, Italy.

Parkinson's disease (PD) is a α-synucleinopathy in which intracellular aggregates of α-synuclein (α-syn) result in neurodegeneration and in the impairment of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex-mediated release of neurotransmitters. SNAP25 is a SNARE complex component: its concentration is increased in the cerebrospinal fluid of PD patients and this is related to the severity of cognitive and motor symptoms. Five SNAP25 single-nucleotide polymorphisms (SNPs) that modulate gene expression and were described to play a role in neurologic conditions (rs363050, rs363039, rs363043, rs3746544, and rs1051312) were analyzed in a cohort of 412 sporadic Italian PD patients and 1103 healthy controls (HC) in order to identify possible correlation with the disease. The SNAP25 rs1051312 C allele and CC genotype confer protection against PD onset, in particular in males (p = 0.003, OR(95%CI) = 0.67(0.51-0.88)) (p = 0.008, OR(95%CI) = 0.28(0.10-0.70)). Co-segregation analyses revealed that the rs1051312 effect was reinforced when present within the rs363043 C-rs3746544 T-rs1051312 C haplotype (p = 3.3 × 10, OR = 0.47, 95%CI = 0.31-0.72), once again in males. Finally, rs363039 influenced age at onset (p = 0.02) and MMSE (Mini-Mental State Examination) scores (p = 0.01). The SNAP25 SNPs analyzed herein modulate gene expression at different levels as they are involved in binding miRNA and transcription factors; this suggests a possible synergistic effect of SNAP25 SNPs in the pathogenesis of PD. A replication in a larger and independent sample will help to further explore this hypothesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-018-1386-0DOI Listing
June 2019

Short-term cortical synaptic depression/potentiation mechanisms in chronic migraine patients with or without medication overuse.

Cephalalgia 2019 02 19;39(2):237-244. Epub 2018 Jun 19.

5 G. B. Bietti Foundation IRCCS, Research Unit of Neurophysiology of Vision and Neurophthalmology, Rome, Italy.

Objective: To study the effects of trains of repetitive transcranial magnetic stimulation (rTMS) over the motor cortex in patients with chronic migraine (CM) with or without medication overuse (MOH).

Subjects And Methods: Thirty-two patients (CM [n = 16]; MOH [n = 16]) and 16 healthy volunteers (HVs) underwent rTMS recording. Ten trains of 10 stimuli each (120% resting motor threshold) were applied over the left motor cortex at 1 Hz or 5 Hz in random order. The amplitude of motor evoked potential (MEP) was evaluated from electromyographic recording in the first dorsal interosseous muscle. The slope of the linear regression line for the 10 stimuli for each participant was calculated using normalized data.

Results: rTMS-1 Hz had a normal depressive effect on MEP amplitude in all groups. rTMS-5 Hz depressed instead of potentiating MEP amplitudes in MOH patients, with a significantly different response from that in HVs and CM patients. The slope of the linear regression of MEP amplitudes was negatively correlated with pain intensity in CM patients, and with the duration of overuse headache in MOH patients.

Conclusions: This different plastic behaviour suggests that MOH and CM, despite exhibiting a similar clinical phenotype, have different neurophysiological learning processes, probably related to different pathophysiological mechanisms of migraine chronification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0333102418784747DOI Listing
February 2019

Efficacy of Modified Atkins Ketogenic Diet in Chronic Cluster Headache: An Open-Label, Single-Arm, Clinical Trial.

Front Neurol 2018 12;9:64. Epub 2018 Feb 12.

Department of Medico-Surgical Sciences and Biotechnologies, "Sapienza" University of Rome Polo Pontino, Latina, Italy.

Introduction: Drug-resistant cluster headache (CH) is still an open clinical challenge. Recently, our group observed the clinical efficacy of a ketogenic diet (KD), usually adopted to treat drug-resistant epilepsies, on migraine.

Aim: Here, we aim to detect the effect of KD in a group of drug-resistant chronic CH (CCH) patients.

Materials And Methods: Eighteen drug-resistant CCH patients underwent a 12-week KD (Modified Atkins Diet, MAD), and the clinical response was evaluated in terms of response (≥50% attack reduction).

Results: Of the 18 CCH patients, 15 were considered responders to the diet (11 experienced a full resolution of headache, and 4 had a headache reduction of at least 50% in terms of mean monthly number of attacks during the diet). The mean monthly number of attacks for each patient at the baseline was 108.71 (SD = 81.71); at the end of the third month of diet, it was reduced to 31.44 (SD = 84.61).

Conclusion: We observed for the first time that a 3-month ketogenesis ameliorates clinical features of CCH.

Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03244735.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2018.00064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816269PMC
February 2018

TNF-α -308 G/A and -238 G/A promoter polymorphisms and sporadic Parkinson's disease in an Italian cohort.

J Neurol Sci 2018 02 11;385:45-48. Epub 2017 Dec 11.

Don Carlo Gnocchi Onlus Foundation, IRCCS, Milano, Italy; Department of Pathophisiology and Transplantation, University of Milan, Milano, Italy.

The etiology of sporadic Parkinson's disease is (PD) still not understood but it is believed that a complex interplay between environmental and genetic factors could trigger the pathology. Pro-inflammatory TNF-α is released by activated microglia and is up-regulated in the brain and cerebrospinal fluid of PD patients; TNF-α modulates neuroinflammation and can activate the molecular mechanisms that lead to neurotoxicity and neuronal death. We analyzed two functional SNPs within the TNF-α gene promoter (rs361525 and rs1800629) in 354 Italian PD patients and 443 healthy controls (HC). In our cohort of patients, no significant associations could be observed between rs361525 and rs1800629 SNPs and either PD onset risk or PD-associated clinical parameters including age at onset of fluctuations, UPDRS-ME (Unified Parkinson Disease Rating Scale-Motor Examination), Schwab & England, Hohen & Yahr stage scale, and MMSE (Mini-Mental State Examination) score. Conflicting results on the role played by TNF-α rs1800629 SNP on PD onset risk are present in the literature. We could not find any association between TNF-α rs361525 and rs1800629 and PD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2017.12.011DOI Listing
February 2018

Cerebral gray matter volume in patients with chronic migraine: correlations with clinical features.

J Headache Pain 2017 Dec 8;18(1):115. Epub 2017 Dec 8.

Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino, Latina, Italy.

Background: To date, few MRI studies have been performed in patients affected by chronic migraine (CM), especially in those without medication overuse. Here, we performed magnetic resonance imaging (MRI) voxel-based morphometry (VBM) analyses to investigate the gray matter (GM) volume of the whole brain in patients affected by CM. Our aim was to investigate whether fluctuations in the GM volumes were related to the clinical features of CM.

Methods: Twenty untreated patients with CM without a past medical history of medication overuse underwent 3-Tesla MRI scans and were compared to a group of 20 healthy controls (HCs). We used SPM12 and the CAT12 toolbox to process the MRI data and to perform VBM analyses of the structural T1-weighted MRI scans. The GM volume of patients was compared to that of HCs with various corrected and uncorrected thresholds. To check for possible correlations, patients' clinical features and GM maps were regressed.

Results: Initially, we did not find significant differences in the GM volume between patients with CM and HCs (p < 0.05 corrected for multiple comparisons). However, using more-liberal uncorrected statistical thresholds, we noted that compared to HCs, patients with CM exhibited clusters of regions with lower GM volumes including the cerebellum, left middle temporal gyrus, left temporal pole/amygdala/hippocampus/pallidum/orbitofrontal cortex, and left occipital areas (Brodmann areas 17/18). The GM volume of the cerebellar hemispheres was negatively correlated with the disease duration and positively correlated with the number of tablets taken per month.

Conclusion: No gross morphometric changes were observed in patients with CM when compared with HCs. However, using more-liberal uncorrected statistical thresholds, we observed that CM is associated with subtle GM volume changes in several brain areas known to be involved in nociception/antinociception, multisensory integration, and analgesic dependence. We speculate that these slight morphometric impairments could lead, at least in a subgroup of patients, to the development and continuation of maladaptive acute medication usage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s10194-017-0825-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762618PMC
December 2017

Anodal transcranial direct current stimulation over the left temporal pole restores normal visual evoked potential habituation in interictal migraineurs.

J Headache Pain 2017 Dec 19;18(1):70. Epub 2017 Jul 19.

G. B. Bietti Foundation IRCCS, Research Unit of Neurophysiology of Vision and Neuro-Ophthalmology, Rome, Italy.

Background: Neuroimaging data has implicated the temporal pole (TP) in migraine pathophysiology; the density and functional activity of the TP were reported to fluctuate in accordance with the migraine cycle. Yet, the exact link between TP morpho-functional abnormalities and migraine is unknown. Here, we examined whether non-invasive anodal transcranial direct current stimulation (tDCS) ameliorates abnormal interictal multimodal sensory processing in patients with migraine.

Methods: We examined the habituation of visual evoked potentials and median nerve somatosensory evoked potentials (SSEP) before and immediately after 20-min anodal tDCS (2 mA) or sham stimulation delivered over the left TP in interictal migraineurs.

Results: Prior to tDCS, interictal migraineurs did not exhibit habituation in response to repetitive visual or somatosensory stimulation. After anodal tDCS but not sham stimulation, migraineurs exhibited normal habituation responses to visual stimulation; however, tDCS had no effect on SSEP habituation in migraineurs.

Conclusion: Our study shows for the first time that enhancing excitability of the TP with anodal tDCS normalizes abnormal interictal visual information processing in migraineurs. This finding has implications for the role of the TP in migraine, and specifically highlights the ventral stream of the visual pathway as a pathophysiological neural substrate for abnormal visual processing in migraine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s10194-017-0778-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517389PMC
December 2017

Use of dynamic movement orthoses to improve gait stability and trunk control in ataxic patients.

Eur J Phys Rehabil Med 2017 Oct 19;53(5):735-743. Epub 2017 Jun 19.

Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University, Polo Pontino, Latina, Italy.

Background: Patients with cerebellar ataxia show increased upper body movements, which have an impact on balance and walking.

Aim: In this study, we investigated the effect of using dynamic movement orthoses (DMO), designed as elastic suits, on trunk motion and gait parameters.

Design: Longitudinal uncontrolled study.

Setting: Outpatient rehabilitation unit.

Population: Eleven patients (7 men, 4 women; mean age: 49.9±9.5 years) with degenerative cerebellar ataxia were enrolled in this study.

Methods: Linear overground gait of patients was recorded by means of an optoelectronic gait analysis system before DMO use (DMO-) and during DMO use (DMO+). Time-distance parameters, lower limb joint kinematics, body sway, trunk oscillations, and gait variability (coefficient of variation [CV]) were recorded. Patient satisfaction with DMO device was measured using Quebec user evaluation of satisfaction with assistive technology.

Results: When using the DMO, patients showed a significant decrease in stance phase duration, double support phase duration, swing phase CV, pelvic range of motion (ROM), body sway, and trunk ROMs. A significant increase was observed in the swing phase duration and knee joint ROM. Out of 11 patients, 10 were either quite satisfied (8 points) or very satisfied (2 points) with the assistive device.

Conclusions: The DMO reduce the upper body motion and in improve balance-related gait parameters.

Clinical Rehabilitation Impact: We propose use of DMO as an assistive/rehabilitative device in the neurorehabilitation of cerebellar ataxia to improve the trunk control and gait stability. DMO may be considered a prototype that can be modified in terms of material characteristics, textile layers, elastic components, and diagonal and lateral seams.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S1973-9087.17.04480-XDOI Listing
October 2017

Resting state connectivity between default mode network and insula encodes acute migraine headache.

Cephalalgia 2018 04 12;38(5):846-854. Epub 2017 Jun 12.

4 "Sapienza" University of Rome Polo Pontino, Department of Medico-surgical Sciences and Biotechnologies, Latina, Italy.

Background Previous functional MRI studies have revealed that ongoing clinical pain in different chronic pain syndromes is directly correlated to the connectivity strength of the resting default mode network (DMN) with the insula. Here, we investigated seed-based resting state DMN-insula connectivity during acute migraine headaches. Methods Thirteen migraine without aura patients (MI) underwent 3 T MRI scans during the initial six hours of a spontaneous migraine attack, and were compared to a group of 19 healthy volunteers (HV). We evaluated headache intensity with a visual analogue scale and collected seed-based MRI resting state data in the four core regions of the DMN: Medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), and left and right inferior parietal lobules (IPLs), as well as in bilateral insula. Results Compared to HV, MI patients showed stronger functional connectivity between MPFC and PCC, and between MPFC and bilateral insula. During migraine attacks, the strength of MPFC-to-insula connectivity was negatively correlated with pain intensity. Conclusion We show that greater subjective intensity of pain during a migraine attack is associated with proportionally weaker DMN-insula connectivity. This is at variance with other chronic extra-cephalic pain disorders where the opposite was found, and may thus be a hallmark of acute migraine head pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0333102417715230DOI Listing
April 2018

Molecular bases of neurophysiologic dysfunctions in migraine.

J Headache Pain 2015 Dec;16(Suppl 1):A15

Don Carlo Gnocchi Onlus Foundation, Rome, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1129-2377-16-S1-A15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759107PMC
December 2015

Obesity, diet and nutraceuticals.

J Headache Pain 2015 Dec;16(Suppl 1):A28

Department of Neurophysiology of Vision and Neurophthalmology, G.B. Bietti Foundation-IRCCS, Rome, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1129-2377-16-S1-A28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759243PMC
December 2015

Molecular genotype in migraine.

J Headache Pain 2015 Dec;16(Suppl 1):A30

Molecular Medicine, IRCCS Stella Maris, Pisa, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1129-2377-16-S1-A30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759105PMC
December 2015