Publications by authors named "Davide Di Lenola"

13 Publications

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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.
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http://dx.doi.org/10.1186/s10194-020-01104-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164277PMC
April 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).
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http://dx.doi.org/10.1186/s12883-019-1351-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588932PMC
June 2019

The association between migraine and physical exercise.

J Headache Pain 2018 Sep 10;19(1):83. Epub 2018 Sep 10.

Department of Neuromedicine and Movement Science, NTNU Norwegian University of Science and Technology, Trondheim, Norway.

Background: There is an unmet need of pharmacological and non-pharmacological treatment options for migraine patients. Exercise can be used in the treatment of several pain conditions, including. However, what exact role exercise plays in migraine prevention is unclear. Here, we review the associations between physical exercise and migraine from an epidemiological, therapeutical and pathophysiological perspective.

Methods: The review was based on a primary literature search on the PubMed using the search terms "migraine and exercise".

Results: Low levels of physical exercise and high frequency of migraine has been reported in several large population-based studies. In experimental studies exercise has been reported as a trigger factor for migraine as well as migraine prophylaxis. Possible mechanisms for how exercise may trigger migraine attacks, include acute release of neuropeptides such as calcitonin gene-related peptide or alternation of hypocretin or lactate metabolism. Mechanisms for migraine prevention by exercise may include increased beta-endorphin, endocannabinoid and brain-derived neurotrophic factor levers in plasma after exercise.

Conclusion: In conclusion, it seems that although exercise can trigger migraine attacks, regular exercise may have prophylactic effect on migraine frequency. This is most likely due to an altered migraine triggering threshold in persons who exercise regularly. However, the frequency and intensity of exercise that is required is still an open question, which should be addressed in future studies to delineate an evidence-based exercise program to prevent migraine in sufferers.
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http://dx.doi.org/10.1186/s10194-018-0902-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134860PMC
September 2018

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

O017. Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet (KD) in migraine: a multimodal evoked potentials study.

J Headache Pain 2015 Dec;16(Suppl 1):A58

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

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http://dx.doi.org/10.1186/1129-2377-16-S1-A58DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759331PMC
December 2015

O025. Excitability of the motor cortex in migraine changes with the distance from the last attack.

J Headache Pain 2015 Dec;16(Suppl 1):A158

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

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http://dx.doi.org/10.1186/1129-2377-16-S1-A158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759334PMC
December 2015

O024. Transcutaneous supraorbital nerve stimulation enhances somatosensory thalamic activity in migraine between attacks: a central mechanism of clinical efficacy?

J Headache Pain 2015 Dec;16(Suppl 1):A160

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

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http://dx.doi.org/10.1186/1129-2377-16-S1-A160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759145PMC
December 2015

Excitability of the motor cortex in patients with migraine changes with the time elapsed from the last attack.

J Headache Pain 2017 Dec 6;18(1). Epub 2017 Jan 6.

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

Background: Motor-evoked potentials (MEPs) produced by single-pulse transcranial magnetic stimulation (TMS) of the motor cortex can be an objective measure of cortical excitability. Previously, MEP thresholds were found to be normal, increased, or even reduced in patients with migraine. In the present study, we determined whether the level of cortical excitability changes with the time interval from the last migraine attack, thereby accounting for the inconsistencies in previous reports.

Methods: Twenty-six patients with untreated migraine without aura (MO) underwent a MEP study between attacks. Their data were then compared to the MEP data collected from a group of 24 healthy volunteers (HVs). During the experiment, the TMS figure-of-eight coil was positioned over the left motor area. After identifying the resting motor threshold (RMT), we delivered 10 single TMS pulses (rate: 0.1 Hz, intensity: 120% of the RMT) and averaged the resulting MEP amplitudes.

Results: The mean RMTs and MEP amplitudes were not significantly different between the MO and HV groups. In patients with MO, the RMTs were negatively correlated with the number of days elapsed since the last migraine attack (rho = -0.404, p = 0.04).

Conclusion: Our results suggest that the threshold for evoking MEPs is influenced by the proximity of an attack; specifically, the threshold is lower when a long time interval has passed after an attack, and is higher (within the range of normative values) when measured close to an attack. These dynamic RMT variations resemble those we reported previously for visual and somatosensory evoked potentials and may represent time-dependent plastic changes in brain excitability in relation to the migraine cycle.
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http://dx.doi.org/10.1186/s10194-016-0712-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5218956PMC
December 2017

Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: a multimodal evoked potentials study.

J Headache Pain 2016 31;17:58. Epub 2016 May 31.

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

Background: Here, we aim to identify cortical electrofunctional correlates of responsiveness to short-lasting preventiveintervention with ketogenic diet (KD) in migraine.

Methods: Eighteen interictal migraineurs underwent visual (VEPs) and median nerve somatosensory (SSEPs) evokedpotentials before and after 1 month of KD during ketogenesis. We measured VEPs N1-P1 and SSEPs N20-P25 amplitudes respectively in six and in two sequential blocks of 100 sweeps as well as habituation as theslope of the linear regression between block 1 to 6 for VEPs or between 1 to 2 for SSEPs.

Results: After 1-month of KD, a significant reduction in the mean attack frequency and duration was observed (all P< 0.001). The KD did not change the 1st SSEP and VEP block of responses, but significantly inducednormalization of the interictally reduced VEPs and SSEPs (all p < 0.01) habituation during the subsequentblocks.

Conclusions: KD could restore normal EPs habituation curves during stimulus repetition without significantly changing theearly amplitude responses. Thus, we hypothesize that KD acts on habituation regulating the balancebetween excitation and inhibition at the cortical level.
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http://dx.doi.org/10.1186/s10194-016-0650-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887398PMC
October 2016

Visual evoked potentials in subgroups of migraine with aura patients.

J Headache Pain 2015 2;16:92. Epub 2015 Nov 2.

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

Background: Patients suffering from migraine with aura can have either pure visual auras or complex auras with sensory disturbances and dysphasia, or both. Few studies have searched for possible pathophysiological differences between these two subgroups of patients.

Methods: Methods - Forty-seven migraine with aura patients were subdivided in a subgroup with exclusively visual auras (MA, N = 27) and another with complex neurological auras (MA+, N = 20). We recorded pattern-reversal visual evoked potentials (VEP: 15 min of arc cheques, 3.1 reversal per second, 600 sweeps) and measured amplitude and habituation (slope of the linear regression line of amplitude changes from the 1st to 6th block of 100 sweeps) for the N1-P1 and P1-N2 components in patients and, for comparison, in 30 healthy volunteers (HV) of similar age and gender distribution.

Results: VEP N1-P1 habituation, i.e. amplitude decrement between 1st and 6th block, which was obvious in most HV (mean slope -0.50), was deficient in both MA (slope +0.01, p = 0.0001) and MA+ (-0.0049, p = 0.001) patients. However, VEP N1-P1 amplitudes across blocks were normal in MA patients, while they were significantly greater in MA+ patients than in HVs.

Conclusions: Our findings suggest that in migraine with aura patients different aura phenotypes may be underpinned by different pathophysiological mechanisms. Pre-activation cortical excitability could be higher in patients with complex neurological auras than in those having pure visual auras or in healthy volunteers.
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http://dx.doi.org/10.1186/s10194-015-0577-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630240PMC
May 2016

Lateral inhibition in the somatosensory cortex during and between migraine without aura attacks: Correlations with thalamocortical activity and clinical features.

Cephalalgia 2016 May 6;36(6):568-78. Epub 2015 Oct 6.

"Sapienza" University of Rome Polo Pontino Department of Medical and Surgical Sciences and Biotechnologies, Italy INM Neuromed IRCCS, Italy.

Background: We studied lateral inhibition in the somatosensory cortex of migraineurs during and between attacks, and searched for correlations with thalamocortical activity and clinical features.

Participants And Methods: Somatosensory evoked potentials (SSEP) were obtained by electrical stimulation of the right median (M) or ulnar (U) nerves at the wrist or by simultaneous stimulation of both nerves (MU) in 41 migraine without aura patients, 24 between (MO), 17 during attacks, and in 17 healthy volunteers (HVs). We determined the percentage of lateral inhibition of the N20-P25 component by using the formula [(100)-MU/(M + U)*100]. We also studied high-frequency oscillations (HFOs) reflecting thalamocortical activation.

Results: In migraine, both lateral inhibition (MO 27.9% vs HVs 40.2%; p = 0.009) and thalamocortical activity (MO 0.5 vs HVs 0.7; p = 0.02) were reduced between attacks, but not during. In MO patients, the percentage of lateral inhibition negatively correlated with days elapsed since the last migraine attack (r = -0.510, p = 0.01), monthly attack duration (r = -0.469, p = 0.02) and severity (r = -0.443, p = 0.03), but positively with thalamocortical activity (r = -0.463, p = 0.02).

Conclusions: We hypothesize that abnormal migraine cycle-dependent dynamics of connectivity between subcortical and cortical excitation/inhibition networks may contribute to clinical features of MO and recurrence of attacks.
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http://dx.doi.org/10.1177/0333102415610873DOI Listing
May 2016

Evidence for brain morphometric changes during the migraine cycle: a magnetic resonance-based morphometry study.

Cephalalgia 2015 Aug 20;35(9):783-91. Epub 2014 Nov 20.

IRCCS Neuromed, Pozzilli (IS), Italy.

Neurophysiological investigations have demonstrated that there are unique fluctuations in the migraine brain functional activity between the ictal and interictal periods. Here we investigated the possibility that there are fluctuations over time also in whole brain morphometry of patients affected by episodic migraine without aura (MO).Twenty-four patients with untreated MO underwent 3T MRI scans during (n = 10) or between attacks (n = 14) and were compared to a group of 15 healthy volunteers (HVs). We then performed voxel-based-morphometry (VBM) analysis of structural T1-weighted MRI scans to determine if changes in brain structure were observed over the course of the migraine cycle.Interictally, MO patients had a significantly lower gray matter (GM) density within the right inferior parietal lobule, right temporal inferior gyrus, right superior temporal gyrus, and left temporal pole than did HVs. Ictally, GM density increased within the left temporal pole, bilateral insula, and right lenticular nuclei, but no areas exhibited decreased GM density.These morphometric GM changes between ictal and interictal phases suggest that abnormal structural plasticity may be an important mechanism of migraine pathology. Given the functional neuroanatomy of these areas, our findings suggest that migraine is a condition associated with global dysfunction of multisensory integration and memory processing.
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http://dx.doi.org/10.1177/0333102414559732DOI Listing
August 2015

Lateralized nociceptive blink reflex habituation deficit in episodic cluster headache: Correlations with clinical features.

Cephalalgia 2015 Jun 16;35(7):600-7. Epub 2014 Sep 16.

IRCCS-Neuromed, Pozzilli (IS), Italy.

Background: We previously observed impaired habituation mechanisms of the conventional blink reflex (BR) in patients with episodic cluster headache (ECH) during the bout, studying only the affected side. Here, we have studied the nociceptive-specific BR (nBR) both on the affected and non-affected sides, and in relation to clinical features.

Participants And Methods: We recorded nBR in 18 ECH patients during the bout, and in 18 healthy volunteers (HVs). We compared pain threshold, area, and habituation of the nBR, recorded both for the affected and non-affected sides.

Results: In patients, the pain threshold on the affected side was lower than that of the non-affected side (p = 0.009), and lower than in HVs (p = 0.038). Reflex area was decreased on both sides (p < 0.05) compared with HVs, whereas habituation was significantly impaired only on the affected side (p = 0.025 vs. HVs; p = 0.003 vs. non-affected). The habituation slope was positively correlated with the number of days since the onset of the bout and the daily attack frequency.

Conclusions: Our data reflect lateralized pathological variations in craniofacial nociception in ECH patients over the course of the cluster period. We hypothesized that this is due to malfunctioning of mechanisms that regulate hypothalamic activity and descending aminergic controls.
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http://dx.doi.org/10.1177/0333102414550418DOI Listing
June 2015