Publications by authors named "Roberto De Icco"

55 Publications

From DYMUS to DYPARK: Validation of a Screening Questionnaire for Dysphagia in Parkinson's Disease.

Dysphagia 2021 Jul 15. Epub 2021 Jul 15.

Neurorehabilitation Unit, IRCCS Mondino Foundation, Pavia, Italy.

Dysphagia is a common debilitating symptom in people with Parkinson's Disease (PD), adequate screening of swallowing disorders is fundamental. The DYMUS questionnaire has shown very good characteristics for the screening of dysphagia in Multiple Sclerosis, and it might also prove useful for screening dysphagia in PD. The primary aim was to test and validate the DYMUS questionnaire in PD patients. This is an observational multicentric study involving 103 patients affected by PD. All subjects filled in the DYMUS and the Eating Assessment Tool (EAT-10) questionnaires. A subgroup of patients (n = 53) underwent a fiber-optic endoscopic evaluation of swallowing (FEES) and their dysphagia was scored by means of the Dysphagia Outcome Severity Scale (DOSS). DYMUS showed a relatively high level of internal consistency (Cronbach's alpha 0.79). A significant positive correlation was found between the DYMUS and the EAT-10 scores (p < 0.001), while a negative correlation was found between the DYMUS and the DOSS scores (p < 0.001). DYMUS showed a good sensitivity and specificity compared to FEES for detecting dysphagia (area under the curve: 0.82, p < 0.001). The ROC curve analysis showed that a DYMUS score ≥ 6 represents a reliable cut-off for the risk of dysphagia. The DYMUS questionnaire proved to be a reliable screening tool to detect dysphagia in patients suffering from PD. It is easy to understand, it can be self-administered and therefore adequate for adoption in the clinical practice with the more convenient name of DYPARK.
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http://dx.doi.org/10.1007/s00455-021-10332-1DOI Listing
July 2021

Ability of a Set of Trunk Inertial Indexes of Gait to Identify Gait Instability and Recurrent Fallers in Parkinson's Disease.

Sensors (Basel) 2021 May 15;21(10). Epub 2021 May 15.

Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, 04100 Latina, Italy.

The aims of this study were to assess the ability of 16 gait indices to identify gait instability and recurrent fallers in persons with Parkinson's disease (pwPD), regardless of age and gait speed, and to investigate their correlation with clinical and kinematic variables. The trunk acceleration patterns were acquired during the gait of 55 pwPD and 55 age-and-speed matched healthy subjects using an inertial measurement unit. We calculated the harmonic ratios (HR), percent recurrence, and percent determinism (RQAdet), coefficient of variation, normalized jerk score, and the largest Lyapunov exponent for each participant. A value of ≤1.50 for the HR in the antero-posterior direction discriminated between pwPD at Hoehn and Yahr (HY) stage 3 and healthy subjects with a 67% probability, between pwPD at HY 3 and pwPD at lower HY stages with a 73% probability, and it characterized recurrent fallers with a 77% probability. Additionally, HR in the antero-posterior direction was correlated with pelvic obliquity and rotation. RQAdet in the antero-posterior direction discriminated between pwPD and healthy subjects with 67% probability, regardless of the HY stage, and was correlated with stride duration and cadence. Therefore, HR and RQA in the antero-posterior direction can both be used as age- and-speed-independent markers of gait instability.
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http://dx.doi.org/10.3390/s21103449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156709PMC
May 2021

Post-traumatic headache attributed to traumatic brain injury: classification, clinical characteristics, and treatment.

Lancet Neurol 2021 06;20(6):460-469

Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Danish Knowledge Center on Headache Disorders, Glostrup, Denmark; Department of Nervous Diseases of the Institute of Professional Education, IM Sechenov First Moscow State Medical University, Moscow, Russia; Department of Neurology, Azerbaijan Medical University, Baku, Azerbaijan. Electronic address:

Post-traumatic headache is a common sequela of traumatic brain injury and is classified as a secondary headache disorder. In the past 10 years, considerable progress has been made to better understand the clinical features of this disorder, generating momentum to identify effective therapies. Post-traumatic headache is increasingly being recognised as a heterogeneous headache disorder, with patients often classified into subphenotypes that might be more responsive to specific therapies. Such considerations are not accounted for in three iterations of diagnostic criteria published by the International Headache Society. The scarcity of evidence-based approaches has left clinicians to choose therapies on the basis of the primary headache phenotype (eg, migraine and tension-type headache) and that are most compatible with the clinical picture. A concerted effort is needed to address these shortcomings and should include large prospective cohort studies as well as randomised controlled trials. This approach, in turn, will result in better disease characterisation and availability of evidence-based treatment options.
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http://dx.doi.org/10.1016/S1474-4422(21)00094-6DOI Listing
June 2021

Electrical Stimulation of Injected Muscles to Boost Botulinum Toxin Effect on Spasticity: Rationale, Systematic Review and State of the Art.

Toxins (Basel) 2021 04 23;13(5). Epub 2021 Apr 23.

Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37100 Verona, Italy.

Botulinum toxin type A (BoNT-A) represents a first-line treatment for spasticity, a common disabling consequence of many neurological diseases. Electrical stimulation of motor nerve endings has been reported to boost the effect of BoNT-A. To date, a wide range of stimulation protocols has been proposed in the literature. We conducted a systematic review of current literature on the protocols of electrical stimulation to boost the effect of BoNT-A injection in patients with spasticity. A systematic search using the MeSH terms "electric stimulation", "muscle spasticity" and "botulinum toxins" and strings "electric stimulation [mh] OR electrical stimulation AND muscle spasticity [mh] OR spasticity AND botulinum toxins [mh] OR botulinum toxin type A" was conducted on PubMed, Scopus, PEDro and Cochrane library electronic databases. Full-text articles written in English and published from database inception to March 2021 were included. Data on patient characteristics, electrical stimulation protocols and outcome measures were collected. This systematic review provides a complete overview of current literature on the role of electrical stimulation to boost the effect of BoNT-A injection for spasticity, together with a critical discussion on its rationale based on the neurobiology of BoNT-A uptake.
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http://dx.doi.org/10.3390/toxins13050303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146442PMC
April 2021

Telemedicine and Virtual Reality at Time of COVID-19 Pandemic: An Overview for Future Perspectives in Neurorehabilitation.

Front Neurol 2021 25;12:646902. Epub 2021 Mar 25.

Headache Science and Neurorehabilitation Center, Istituto di Ricovero e Cura a Carattere Scientifico Mondino Foundation, Pavia, Italy.

In catastrophic situations such as pandemics, patients' healthcare including admissions to hospitals and emergency services are challenged by the risk of infection and by limitations of healthcare resources. In such a setting, the use of telemedicine interventions has become extremely important. New technologies have proved helpful in pandemics as a solution to improve the quality of life in vulnerable patients such as persons with neurological diseases. Moreover, telemedicine interventions provide at-home solutions allowing clinicians to telemonitor and assess patients remotely, thus minimizing risk of infection. After a review of different studies using telemedicine in neurological patients, we propose a telemedicine process flow for healthcare of subjects with chronic neurological disease to respond to the new challenges for delivering quality healthcare during the transformation of public and private healthcare organizations around the world forced by COVID-19 pandemic contingency. This telemedicine process flow represents a replacement for in-person treatment and thereby the provision equitable access to the care of vulnerable people. It is conceptualized as comprehensive service including (1) teleassistance with patient counseling and medical treatment, (2) telemonitoring of patients' health conditions and any changes over time, as well as (3) telerehabilitation, i.e., interventions to assess and promote body functions, activities, and consecutively participation. The hereby proposed telemedicine process flow could be adopted on a large scale to improve the public health response during healthcare crises like the COVID-19 pandemic but could equally promote equitable health care independent of people's mobility or location with respect to the specialized health care center.
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http://dx.doi.org/10.3389/fneur.2021.646902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027250PMC
March 2021

Spinal nociceptive sensitization and plasma palmitoylethanolamide levels during experimentally-induced migraine attacks.

Pain 2021 Feb 8. Epub 2021 Feb 8.

Headache Science & Neurorehabilitation Center, IRCCS Mondino Foundation, Pavia, Italy Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy Department of Drug Discovery and Development, Istituto Italiano di Tecnologia, Genova, Italy.

Abstract: Migraine pathophysiology has been suggested to include dysregulation of the endocannabinoid system (ES). We simultaneously evaluated plasma anandamide (AEA) and palmitoylethanolamide (PEA) levels and spinal sensitization in a validated human model of migraine based on systemic nitroglycerin (NTG) administration.Twenty-four subjects with episodic migraine (MIG) and 19 healthy controls (HC) underwent blood sampling and investigation of nociceptive withdrawal reflex thresholds (RTh: single-stimulus threshold; TST: temporal summation threshold) before and 30 (T30), 60 (T60) and 120 (T120) minutes after sublingual NTG administration (0.9 mg).At baseline, the MIG and HC groups were comparable for plasma AEA (p=0.822) and PEA (p=0.182) levels, and for RTh (p=0.142) and TST values (p=0.150). AEA levels increased after NTG administration (p=0.022) in both groups, without differences between them (p=0.779). By contrast, after NTG administration, PEA levels increased in the MIG group at T120 (p=0.004), while remaining stable in the HC group.NTG administration induced central sensitization in the MIG group, which was recorded as reductions in RTh (p=0.046) at T30 and T120, and in TST (p=0.001) at all time points. In the HC group we observed increases in RTh (p=0.001) and TST (p=0.008), which suggests the occurrence of habituation. We found no significant correlations between the ES and neurophysiological parameters.Our findings suggest a role for PEA in the ictal phase of episodic migraine. The ES does not seem to be directly involved in the modulation of NTG-induced central sensitization, which suggests that the observed PEA increase and spinal sensitization are parallel, probably unrelated, phenomena.
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http://dx.doi.org/10.1097/j.pain.0000000000002223DOI Listing
February 2021

Thalamocortical Connectivity in Experimentally-Induced Migraine Attacks: A Pilot Study.

Brain Sci 2021 Jan 27;11(2). Epub 2021 Jan 27.

Headache Science Center, IRCCS Mondino Foundation, 27100 Pavia, Italy.

In this study we used nitroglycerin (NTG)-induced migraine attacks as a translational human disease model. Static and dynamic functional connectivity (FC) analyses were applied to study the associated functional brain changes. A spontaneous migraine-like attack was induced in five episodic migraine (EM) patients using a NTG challenge. Four task-free functional magnetic resonance imaging (fMRI) scans were acquired over the study: baseline, prodromal, full-blown, and recovery. Seed-based correlation analysis (SCA) was applied to fMRI data to assess static FC changes between the thalamus and the rest of the brain. Wavelet coherence analysis (WCA) was applied to test time-varying phase-coherence changes between the thalamus and salience networks (SNs). SCA results showed significantly FC changes between the right thalamus and areas involved in the pain circuits (insula, pons, cerebellum) during the prodromal phase, reaching its maximal alteration during the full-blown phase. WCA showed instead a loss of synchronisation between thalami and SN, mainly occurring during the prodrome and full-blown phases. These findings further support the idea that a temporal change in thalamic function occurs over the experimentally induced phases of NTG-induced headache in migraine patients. Correlation of FC changes with true clinical phases in spontaneous migraine would validate the utility of this model.
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http://dx.doi.org/10.3390/brainsci11020165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911420PMC
January 2021

A systematic review, meta-analysis and meta-regression evaluating the adverse reactions to erenumab in the preventive treatment of migraine.

Expert Opin Drug Saf 2021 Apr 29;20(4):467-474. Epub 2020 Dec 29.

Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.

: Erenumab has recently been approved as a pharmacological treatment for the prevention of migraine. However, the incidence estimates of adverse drug reactions (ADRs) were not consistent among studies. Consequently, pooled measures of the incidences of ADRs that accounts for inter-study heterogeneity are desirable. In addition, little is known on the factors leading to such heterogeneity.: Clinical trials evaluating the occurrence of ADRs related to erenumab in migraine patients were searched with Ovid MEDLINE until April 2020. Random intercept models were used to estimate the pooled incidence of the ADRs reported at least in 5 different study populations. To examine whether specific factors correlated with the pooled incidence, we performed random-effects meta-regression.: Of 138 retrieved references, 8 clinical trials were included in the meta-analysis. We observed a significant heterogeneity of the incidence estimates of back pain, influenza, nasopharyngitis, and upper respiratory tract infection (URTI). Most of the observed heterogeneity is ascribed to treatment duration for back pain ( = 0.045), influenza ( < 0.001) and URTI ( < 0.001), and significantly attributed to Body Mass Index (BMI) for nasopharyngitis ( < 0.001).: Back pain, influenza, nasopharyngitis and URTI showed a significant heterogeneity of incidence estimates.
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http://dx.doi.org/10.1080/14740338.2021.1866537DOI Listing
April 2021

Non-invasive Brain and Spinal Stimulation for Pain and Related Symptoms in Multiple Sclerosis: A Systematic Review.

Front Neurosci 2020 20;14:547069. Epub 2020 Nov 20.

Section of Neurology, Department of Neurosciences, Verona University Hospital, Verona, Italy.

Neuropathic and nociceptive pain frequently affect patients with multiple sclerosis (MS), with a prevalence close to 90% and significant impact on general health and quality of life. Pharmacological strategies are widely used to treat pain in MS, but their effectiveness and side-effects are controversial. Among non-pharmacological treatments for pain, non-invasive brain and spinal stimulation (NIBSS) has shown promising preliminary results in MS. Systematic review to investigate the effect of NIBSS for the management of pain in MS. A literature search using Pubmed, Science Direct and Web of Science was conducted from databases inception to February 21, 2020 for studies assessing the analgesic effect of NIBSS on pain in MS. A total of 279 records were title- and abstract-screened, nine were assessed for full text and included. The NIBSS techniques explored were transcranial direct current stimulation ( = 5), transcranial magnetic stimulation ( = 2), transcranial random noise stimulation ( =1), transcutaneous spinal direct current stimulation ( = 1). The targets were the primary motor cortex (M1; = 4), the left dorsolateral pre-frontal cortex (DLPFC; = 3), the spinal cord ( = 1), unspecified brain target ( = 1). The study designs were randomized ( = 7), open label ( = 1), single case report ( = 1). Despite the differences in study design, target and NIBSS technique that impeded a meta-analysis, all the studies converge in showing a significant improvement of pain after active NIBSS with less consistent effects on other symptoms of the pain-related cluster (depression, fatigue, cognition) and quality of life. Excitatory NIBSS over M1, left DLPFC and spinal cord appear to be the most effective protocols for pain in MS. Open questions include the use of neurophysiological or neuroimaging surrogate outcome measures, the stratification of patients according to the clinical profiles and underlying pathogenetic mechanisms and the combination of NIBSS to pharmacological treatment, neurorehabilitation, or psychotherapy to improve the clinical effect. The duration of the effect to NIBSS and the feasibility and efficacy of telemedicine NIBSS protocols are other open key questions.
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http://dx.doi.org/10.3389/fnins.2020.547069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715002PMC
November 2020

Characterization of the peripheral FAAH inhibitor, URB937, in animal models of acute and chronic migraine.

Neurobiol Dis 2021 01 28;147:105157. Epub 2020 Oct 28.

Translational Neurovascular Research Unit, Headache Science Centre, IRCCS Mondino Foundation, via Mondino 2, 27100 Pavia, Italy; Department of Brain and Behavioral Sciences, University of Pavia, via Bassi 21, 27100 Pavia, Italy.

Inhibiting the activity of fatty-acid amide hydrolase (FAAH), the enzyme that deactivates the endocannabinoid anandamide, enhances anandamide-mediated signaling and holds promise as a molecular target for the treatment of human pathologies such as anxiety and pain. We have previously shown that the peripherally restricted FAAH inhibitor, URB937, prevents nitroglycerin-induced hyperalgesia - an animal model of migraine - and attenuates the activation of brain areas that are relevant for migraine pain, e.g. trigeminal nucleus caudalis and locus coeruleus. The current study is aimed at profiling the behavioral and biochemical effects of URB937 in animal models of acute and chronic migraine. We evaluated the effects of URB937 in two rat models that capture aspects of acute and chronic migraine, and are based on single or repeated administration of the vasodilating drug, nitroglycerin (NTG). In addition to nocifensive behavior, in trigeminal ganglia and medulla, we measured mRNA levels of neuropeptides and pro-inflammatory cytokines along with tissue levels of anandamide and palmitoylethanolamide (PEA), an endogenous agonist of peroxisome proliferator-activated receptor type-a (PPAR-a), which is also a FAAH substrate. In the acute migraine model, we also investigated the effect of subtype-selective antagonist for cannabinoid receptors 1 and 2 (AM251 and AM630, respectively) on nocifensive behavior and on levels of neuropeptides and pro-inflammatory cytokines. In the acute migraine paradigm, URB937 significantly reduced hyperalgesia in the orofacial formalin test when administered either before or after NTG. This effect was accompanied by an increase in anandamide and PEA levels in target neural tissue, depended upon CB1 receptor activation, and was associated with a decrease in calcitonin gene-related peptide (CGRP), substance P and cytokines TNF-alpha and IL-6 mRNA. Similar effects were observed in the chronic migraine paradigm, where URB937 counteracted NTG-induced trigeminal hyperalgesia and prevented the increase in neuropeptide and cytokine transcription. The results show that peripheral FAAH inhibition by URB937 effectively reduces both acute and chronic NTG-induced trigeminal hyperalgesia, likely via augmented anandamide-mediated CB1 receptor activation. These effects are associated with inhibition of neuropeptidergic and inflammatory pathways.
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http://dx.doi.org/10.1016/j.nbd.2020.105157DOI Listing
January 2021

Migraine neuroscience: from experimental models to target therapy.

Neurol Sci 2020 Dec;41(Suppl 2):351-361

Headache Science and Neurorehabilitation Centre, IRCCS Mondino Foundation, Pavia, Italy.

Migraine sciences have witnessed tremendous advances in recent years. Pre-clinical and clinical experimental models have contributed significantly to provide useful insights into the brain structures that mediate migraine attacks. These models have contributed to elucidate the role of neurotransmission pathways and to identify the role of important molecules within the complex network involved in migraine pathogenesis. The contribution and efforts of several research groups from all over the world has ultimately lead to the generation of novel therapeutic approaches, specifically targeted for the prevention of migraine attacks, the monoclonal antibodies directed against calcitonin gene-related peptide or its receptor. These drugs have been validated in randomized placebo-controlled trials and are now ready to improve the lives of a large multitude of migraine sufferers. Others are in the pipeline and will soon be available.
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http://dx.doi.org/10.1007/s10072-020-04808-5DOI Listing
December 2020

Plasma levels of CGRP and expression of specific microRNAs in blood cells of episodic and chronic migraine subjects: towards the identification of a panel of peripheral biomarkers of migraine?

J Headache Pain 2020 Oct 16;21(1):122. Epub 2020 Oct 16.

Headache Science & Neurorehabilitation, IRCCS Mondino Foundation, Pavia, Italy.

Background: Migraine can manifest with an episodic or a chronic pattern in a continuum of disease severity. Multiple factors are associated with the progression of the pattern from episodic to chronic. One of the most consistently reported factors is the overuse of medications (MO) for the acute treatment of migraine attacks. The mechanisms through which MO facilitates the transformation of episodic migraine (EM) into chronic migraine (CM) are elusive. In order to provide insights into these mechanisms, the present study aims to identify possible peripheral biomarkers associated with the two forms of migraine, and with the presence of MO.

Methods: We evaluated the plasma levels of calcitonin gene-related peptide (CGRP) and the expression of miR-34a-5p and miR-382-5p in peripheral blood mononuclear cells of subjects with EM (n = 27) or CM-MO (n = 28). Subjects in the CM-MO group were also tested 2 months after an in-hospital detoxification protocol.

Results: CGRP, miR-382-5p, and miR-34a-5p levels were significantly higher in CM-MO subjects when compared to EM patients (p = 0.003 for all comparisons). After correcting for age, sex, and disease duration, miRNAs expression was still significantly associated with migraine phenotype (EM vs. CM-MO: p = 0.014 for miR-382-5p, p = 0.038 for miR-34a-5p), while CGRP levels were not (p = 0.115). CGRP plasma levels significantly and positively correlated with miR-382-5p (Spearman's rho: 0.491, p = 0.001) and miR-34a-5p (Spearman's rho: 0.303, p =0.025) in the overall population. In the CM-MO group, detoxification significantly decreased CGRP levels and miRNAs expression (p = 0.001). When comparing responders and non-responders to the detoxification, the former group (n = 23) showed significantly higher levels of CGRP at baseline, and significantly lower expression of miR-382-5p after the detoxification.

Conclusions: Our findings identify a potential panel of peripheral markers associated with migraine subtypes and disease severity. CGRP levels as well as miRNAs expression were influenced by MO, and modulated by detoxification in subjects with CM-MO.

Trial Registration: The study protocol was registered at www.clinicaltrials.gov ( NCT04473976 ).
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http://dx.doi.org/10.1186/s10194-020-01189-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565351PMC
October 2020

Peripheral changes of endocannabinoid system components in episodic and chronic migraine patients: A pilot study.

Cephalalgia 2021 02 23;41(2):185-196. Epub 2020 Sep 23.

Headache Science Centre, IRCCS Mondino Foundation, Pavia, Italy.

Background: Preclinical and clinical evidence suggests a role for the dysregulation of the endocannabinoid system in migraine pain, particularly in subjects with chronic migraine.

Methods: The gene expression of endocannabinoid system components was assayed in peripheral blood mononuclear cells of 25 subjects with episodic migraine, 26 subjects with chronic migraine with medication overuse (CM-MO) and 24 age-matched healthy controls. We also evaluated the protein expression of cannabinoid receptors 1 and 2 as well as DNA methylation changes in genes involved in endocannabinoid system components.

Results: Both episodic migraine and CM-MO subjects showed higher cannabinoid receptor 1 and cannabinoid receptor 2 gene and protein expression compared to controls. Fatty acid amide hydrolase gene expression, involved in anandamide degradation, was lower in migraine groups compared to healthy control subjects. N-arachidonoyl phosphatidylethanolamine phospholipase D gene expression was significantly higher in all migraineurs, as were monoacylglycerol lipase and diacylglycerol lipase gene expressions. The above markers significantly correlated with the number of migraine days and with the days of acute drug intake.

Conclusion: The findings point to transcriptional changes in endocannabinoid system components occurring in migraineurs. These changes were detected peripherally, which make them amenable for a wider adoption to further investigate their role and applicability in the clinical field.clinicaltrials.gov NTC04324710.
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http://dx.doi.org/10.1177/0333102420949201DOI Listing
February 2021

Reducing Episodic Cluster Headaches: Focus on Galcanezumab.

J Pain Res 2020 2;13:1591-1599. Epub 2020 Jul 2.

Danish Headache Center, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

The involvement of calcitonin gene-related peptide in migraine and cluster headache has led to the recent development of new therapies. Galcanezumab, a novel monoclonal antibody targeting the calcitonin gene-related peptide, is approved for the migraine prevention and has recently been tested for the prevention of cluster headache. Two clinical trials have been conducted to investigate the efficacy and safety of galcanezumab in episodic cluster headache and chronic cluster headache. While efficacy endpoints were not met in the chronic subtype, galcanezumab reduced the weekly frequency of attacks in patients with episodic cluster headaches. In both studies, the antibody was well tolerated. This review summarizes and critically reviews the available data regarding the rationale behind targeting the calcitonin gene-related peptide with galcanezumab for the prevention of cluster headache.
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http://dx.doi.org/10.2147/JPR.S222604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342329PMC
July 2020

Neurophysiological and biomolecular effects of erenumab in chronic migraine: An open label study.

Cephalalgia 2020 10 26;40(12):1336-1345. Epub 2020 Jul 26.

Headache Science Centre, IRCCS Mondino Foundation, Pavia, Italy.

Introduction: Anti-calcitonin gene-related peptide antibodies proved effective in the preventive treatment of chronic migraine. In this open label study, we aim to assess the effects of erenumab administration on neurophysiological and biomolecular profiles in a representative cohort of chronic migraine patients.

Methods: Forty patients with a history of chronic migraine for at least 12 months prior to enrollment, and previous failure of at least two different preventive therapies, were enrolled. After a 1-month observation period (T0), patients were treated with erenumab 70 mg s.c. (every 28 days) for a total of three administrations. At week 12, they returned for the end-of-protocol visit (T3). At T0 and T3, patients underwent recording of clinical features, recording of single stimulus (RTh), temporal summation (TST) thresholds of the nociceptive withdrawal reflex, venous blood sampling for miR-382-5p, and miR-34a-5p quantification.

Results: At T3, 31 patients (77.5%) qualified as 30% Responders (reduction in monthly migraine days by at least 30% in the last 4-week observation period). RTh (T0: 15.4 ± 8.1 mA, T3: 19.7 ± 8.2 mA) as well as TST (T0: 11.2 ± 5.8 mA, T3: 13.4 ± 5.0 mA) significantly increased at T3 in 30% Responders ( = 0.001 for both), while we did not observe significant changes in NON-responder patients. MiR-382-5p and miR-34a-5p levels were significantly lower after erenumab administration in the overall study population ( = 0.015, and  = 0.001, respectively), without significant differences between 30% Responder and NON-responder groups.

Conclusions: Different migraine phenotypes, characterized by different treatment susceptibility, may exist as suggested by the divergent behavior between neurophysiological and biomolecular findings in 30% Responder vs. NON-responder patients.The study protocol was registered at clinicaltrials.gov (NCT04361721).
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http://dx.doi.org/10.1177/0333102420942230DOI Listing
October 2020

Reproducibility and reaction time of swallowing as markers of dysphagia in parkinsonian syndromes.

Clin Neurophysiol 2020 09 9;131(9):2200-2208. Epub 2020 Jul 9.

Clinical Neurophysiology Unit, IRCCS Mondino Foundation, Pavia, Italy.

Objective: To investigate reproducibility and reaction time of oropharyngeal swallowing in patients with Parkinson's disease (PD) and atypical parkinsonisms (APs).

Methods: We enrolled 19 patients with PD, 30 with APs, and 20 healthy subjects. Presence and severity of dysphagia were assessed with clinical and fiberoptic endoscopic evaluations of swallowing. Reproducibility of the oral and pharyngeal phases of swallowing were respectively assessed by calculating the 'similarity index' of the electromyography activity of the submental/suprahyoid muscles and of the laryngeal-pharyngeal mechanogram during consecutive swallows. These were performed both 'on command' and spontaneously. The swallowing reaction time was also recorded.

Results: Reproducibility of the oral phase of swallowing was reduced in patients with dysphagia, mainly when swallowing 'on command'. Swallowing reaction time was prolonged in dysphagic patients. These electrophysiological parameters did not vary among different parkinsonian syndromes and correlated with dysphagia severity.

Conclusions: Increased variability of oral swallowing automatisms and abnormal sensorimotor integration may be of relevance for the pathophysiology of dysphagia in parkinsonian syndromes.

Significance: The electrophysiological assessment represents a valuable tool to investigate swallowing alterations in parkinsonian syndromes. It may also provide useful insights into clinical severity and pathophysiology of dysphagia, giving clues for the choice of the best therapeutic approach.
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http://dx.doi.org/10.1016/j.clinph.2020.06.018DOI Listing
September 2020

Anodal transcranial direct current stimulation and intermittent theta-burst stimulation improve deglutition and swallowing reproducibility in elderly patients with dysphagia.

Neurogastroenterol Motil 2020 05 23;32(5):e13791. Epub 2020 Jan 23.

Clinical Neurophysiology Unit, IRCCS Mondino Foundation, Pavia, Italy.

Background: Dysphagia in the elderly, known as presbydysphagia, has become a relevant public health problem in several countries. Swallowing disorders may be a consequence of different neurological disorders (secondary presbydysphagia) or the expression of the aging process itself (primary presbydysphagia). We aimed to test the therapeutic potential of two different non-invasive brain stimulation (NIBS) techniques in subjects with primary or secondary presbydysphagia.

Methods: A blinded randomized controlled trial with crossover design was carried out in 42 patients, randomly assigned to anodal transcranial direct current stimulation (tDCS) or intermittent theta-burst stimulation (TBS) group. Both tDCS and TBS were applied for 5 consecutive days over the right swallowing motor cortex. The swallowing function was assessed before and 1 and 3 months after the stimulation using the Dysphagia Outcome and Severity Scale (DOSS), scored based on clinical assessment and fiberoptic endoscopic evaluation of swallowing. An electrophysiological method was also applied to evaluate changes in the reproducibility of the swallowing behavior.

Key Results: Both real tDCS and TBS had beneficial effects on the swallowing function in patients with primary and secondary presbydysphagia. Anodal tDCS resulted in an improvement of 0.5 points in DOSS at 1-month follow-up (P = .014), whereas intermittent TBS induced an increase of 0.7 and 0.6 points at 1- and 3-month follow-up evaluations, respectively (P = .0001 and P = .005, respectively). Reproducibility of both the oral and pharyngeal phases of swallowing significantly increased at 1-month follow-up.

Conclusions And Inferences: Our results suggest that non-invasive cortical stimulation may be useful for dysphagia recovery in elderly patients.
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http://dx.doi.org/10.1111/nmo.13791DOI Listing
May 2020

Gender Differences in the Clinical Presentation of Cluster Headache: A Role for Sexual Hormones?

Front Neurol 2019 22;10:1220. Epub 2019 Nov 22.

Headache Science Centre, IRCCS Mondino Foundation, Pavia, Italy.

Cluster Headache (CH) is a well-characterized primary headache that mostly affects men, although a progressive decrease in the male-to-female ratio has occurred over time. Available, but partly discordant, data on gender-related differences in CH suggest a more marked overlapping with migraine features in female subjects. The aim of this study is to carefully evaluate the female/male distribution of the typical migraine-associated symptoms and of other features of the disease in a large and well-characterized clinical population of CH subjects. We enrolled consecutive CH patients regularly followed at the tertiary Headache Science Center of the IRCCS Mondino Foundation of Pavia (Italy) who attended the Center for a CH bout between September 2016 and October 2018. The subjects were requested to fill in a semi-structured questionnaire focused on the presence of migraine-associated symptoms, familiarity for migraine and, for women, the relationship of CH onset with the reproductive events of their life. These data were compared and integrated with those recorded over time in our clinical database, including demographics and clinical characteristics. The primary outcome was the gender distribution of subjects who satisfied ICHD-III criterion D for migraine-associated symptoms. The secondary outcomes were represented by the gender distribution of individual migraine-associated symptoms and of other disease features included in the questionnaire and/or in the clinical database. Data from 163 males (mean age 41.46 ± 10.37) and 87 females suffering of CH (mean age 42.24 ± 11.95) were analyzed. We did not find a different distribution between sexes as regards the primary outcome measure (F 73.6%, M 65.6%, = 0.200). However, when we analyzed the occurrence of individual symptoms, nausea and osmophobia were reported more frequently by women ( = 0.048, = 0.037, respectively). Ptosis and nasal congestion were predominant in females ( = 0.017 and = 0.01, respectively), while enlarged temporal artery was more frequently reported by men ( = 0.001). Distribution of pain across the head tended to be larger in women, extending more frequently to the zygomatic ( = 0.050), parietal ( = 0.049), and frontal ( = 0.037) regions. Women had a longer mean attack duration ( = 0.004) than men. In CH women the onset of disease often corresponded with moments of important changes in the levels of sexual hormones (menarche, post-partum, menopause). Concomitant thyroid diseases and psychiatric disorders were observed more frequently in women than in men, while snoring and smoking habit was reported by a higher percentage of men than women. We confirmed the presence of distinct gender-related differences in CH and added some novel information that lends credibility to the hypothesis of a closer phenotypical similarity between CH and migraine in the female sex. These observations are relevant for advancing our knowledge on CH pathophysiology, as well as for a more refined diagnostic framing and improved management of the disease.
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http://dx.doi.org/10.3389/fneur.2019.01220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882735PMC
November 2019

Experimentally induced spinal nociceptive sensitization increases with migraine frequency: a single-blind controlled study.

Pain 2020 02;161(2):429-438

Headache Science Centre, IRCCS Mondino Foundation, Pavia, Italy.

The nitric-oxide donor nitroglycerin (NTG) administration induces a facilitation of nociceptive pathways in episodic migraine. This study aims to test the hypothesis that induced spinal sensitization could be more pronounced in patients affected by high-frequency migraine (HF-MIG) with respect to low-frequency migraine (LF-MIG). We enrolled 28 patients with LF-MIG (1-5 migraine days/month), 19 patients with HF-MIG (6-14 migraine days/month), and 21 healthy controls (HCs). Spinal sensitization was evaluated with the neurophysiological recording of the temporal summation threshold (TST) of the nociceptive withdrawal reflex at the lower limb. Temporal summation threshold was recorded at baseline and 30, 60, and 120 minutes after NTG administration (0.9 mg sublingual). Spinal sensitization was detected in LF-MIG at 60 (P = 0.010) and 120 minutes (P = 0.001) and in HF-MIG at 30 (P = 0.008), 60 (P = 0.001), and 120 minutes (P = 0.001) after NTG administration. Temporal summation threshold did not change in HC (P = 0.899). Moreover, TST reduction was more pronounced in HF-MIG with respect to LF-MIG (P = 0.002). The percentage of patients who developed a migraine-like headache after NTG was comparable in the 2 migraine groups (LF-MIG: 53.6%, HF-MIG: 52.6%, P = 0.284), whereas no subjects in the HC group developed a delayed-specific headache. Notably, the latency of headache onset was significantly shorter in the HF-MIG group when compared with the LF-MIG group (P = 0.015). Our data demonstrate a direct relationship between migraine frequency and both neurophysiological and clinical parameters, to suggest an increasing derangement of the nociceptive system control as the disease progresses, probably as a result of the interaction of genetic and environmental factors.
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http://dx.doi.org/10.1097/j.pain.0000000000001726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970578PMC
February 2020

Evening melatonin timing secretion in real life conditions in patients with Alzheimer disease of mild to moderate severity.

Sleep Med 2019 11 31;63:122-126. Epub 2019 May 31.

Unit of Sleep Medicine and Epilepsy, IRCCS Mondino Foundation, Via Mondino 2, 27100, Pavia, Italy; Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy.

Background: Circadian dysfunction is thought to take part in the pathogenesis of sleep disorders in Alzheimer's disease (AD) and in AD pathophysiology itself.

Objective: Our study aims to calculate dim light melatonin onset (DLMO) secretion in order to define the circadian phase in patients with AD at an early stage of the disease.

Methods: Twenty-one patients (M/F: 11/10; mean age 74.1 ± 5.4 years; mean disease duration 3.4 ± 1.6 years) with a diagnosis of AD and 17 healthy controls (HC; M/F: 10/7; mean age 67.47 ± 3.8 years) were investigated for subjective nocturnal sleep quality and chronotype, for DLMO and quantitative aspects of the evening melatonin secretion by means of a 5-point in-home evening melatonin saliva test.

Results: Subjective sleep quality score on the Pittsburgh Sleep Quality Index questionnaire (PSQI) above 5 (p = 0.24), insomnia frequency as measured by Sleep Condition Indicator Questionnaire (p = 0.823) and the subjective chronotype according to Morning Evening Questionnaire (MEQ) scores distribution (p = 0.464) did not differ between AD and HC. However, DLMO occurred significantly later (55 min; p = 0.028), and melatonin secretion following DLMO was significantly decreased in AD patients compared to HC.

Conclusion: Initial evening secretion of melatonin proves to be delayed and mildly impaired in patients with a mild/moderate form of Alzheimer disease while patients' subjective sleep parameters and chronotype are reported to be similar to those of HC. These results indicate that subclinical altered patterns of melatonin secretion occur in subjects with AD at an early stage of the disease.
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http://dx.doi.org/10.1016/j.sleep.2019.04.018DOI Listing
November 2019

Clinical Subtypes of Medication Overuse Headache - Findings From a Large Cohort.

Headache 2019 10 3;59(9):1481-1491. Epub 2019 Oct 3.

Headache Science Center, IRCCS Mondino Foundation, Pavia, Italy.

Background: The International Classification of Headache Disorders lists different subtypes of medication overuse headache (MOH), according to the medication overused. The aim of this study is to evaluate whether the different subtypes correspond to clinically distinguishable phenotypes in a large population.

Method: This descriptive cross-sectional observational study included 660 patients with MOH referred to headache centers in Europe and Latin America as a part of the COMOESTAS project. Information about clinical features was collected with structured patient interviews and with self-administered questionnaires for measuring disability, anxiety, and depression.

Results: Female/male ratio, body mass index, marital status, and level of education were similar among in subjects enrolled in the 5 centers. The mean age was higher among subjects overusing triptans (T-MOH) with respect to subjects overusing simple analgesic (A-MOH). Duration of headache before chronification was longer in T-MOH (19.2 ± 11.9 years) and in subjects overusing ergotamines (E-MOH, 17.8 ± 11.7 years) with respect to the A-MOH group (13.1 ± 10.9; P < .001 and P = .017, respectively) and in T-MOH with respect multiple drug classes (M-MOH, 14.9 ± 11.7; P = .030). Migraine Disability Assessment (MIDAS) score was significantly lower in E-MOH group (33.6 ± 41.6), while T-MOH group (56.8 ± 40.6) had a significant lower MIDAS score with respect to M-MOH (67.2 ± 62.5; P = .016 and P = .037, respectively). Prevalence of depression and anxiety was lower in patients overusing T with respect to other groups of patients (χ  = 10.953, P = .027 and χ  = 25.725, P < .001, respectively).

Conclusion: In this study on a large and very well characterized population of MOH, we describe the distinctive clinical characteristics of MOH subtypes. These findings contribute to more clearly define the clinical picture of a poorly delineated headache disorder. They also provide some insights in the possible trajectories leading to this highly disabling chronic headache, that is classified as a secondary form, but whose occurrence is entirely dependent on an underlying primary headache.
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http://dx.doi.org/10.1111/head.13641DOI Listing
October 2019

OnabotulinumtoxinA Reduces Temporal Pain Processing at Spinal Level in Patients with Lower Limb Spasticity.

Toxins (Basel) 2019 06 20;11(6). Epub 2019 Jun 20.

Neurorehabilitation Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy.

Spasticity is a muscle tone disorder associated with different neurological conditions. Spasticity could be associated with pain, high disability, poor functional recovery, and reduced quality of life. Botulinum neurotoxin type A (BoNT-A) is considered a first-line treatment for spasticity and, more recently, it also represents a therapeutic option for various chronic pain conditions. In this open label study, we aim to evaluate the effect of the BoNT-A on the spinal nociception in patients affected by spasticity of the lower limbs with associated pain with predominantly neuropathic features. Ten patients with stroke, 10 with multiple sclerosis and 5 with spinal cord injury were enrolled in the study. They were tested with clinical scales (neuropathic pain scale inventory (NPSI), numerical rating scale (NRS), modified Ashworth scale (MAS) and with the nociceptive withdrawal reflex at lower limbs to explore the spinal temporal summation threshold at baseline and 30 day after BoNT-A injection. OnabotulinumtoxinA (50 to 200 units per site) was injected in the lower limb muscles according to the distribution of spasticity. No significant differences were found at baseline for neurophysiological features across groups. After the BoNT-A injection, we recorded a significant reduction in MAS and NRS scores. Regarding the neurophysiological parameters, we described a significant increase in the temporal summation threshold after the BoNT-A injection. Our data supports the hypothesis that peripherally injected OnabotulinumtoxinA modulates the excitability of spinal cord nociceptive pathways. This activity may take place irrespective of the effect of the drug on spasticity.
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http://dx.doi.org/10.3390/toxins11060359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628414PMC
June 2019

Negative Short-Term Outcome of Detoxification Therapy in Chronic Migraine With Medication Overuse Headache: Role for Early Life Traumatic Experiences and Recent Stressful Events.

Front Neurol 2019 7;10:173. Epub 2019 Mar 7.

Headache Science Centre, IRCCS Mondino Foundation, Pavia, Italy.

Early traumatic experiences and Stressful episodes appear to be associated to the development and perpetuation of chronic pain disorders and to dependence-related behaviors. The present study evaluated whether these factors can be predictors, together with psychiatric conditions, of the outcome of a detoxification treatment in patients suffering from chronic migraine and medication-overuse headache in a 2-month follow-up. Consecutive patients undergoing a detoxification program as therapy for treating chronic migraine and medication overuse headache at the Pavia Headache Center were analyzed. During this program, lasting about 1 week, all patients received the standard CARE in-patient withdrawal protocol, which consisted in discontinuing abruptly the overused drug(s) and receiving daily detoxification therapy. Data on childhood traumatic events and recent stressful ones were analyzed by means of the Childhood Trauma Questionnaire and Stressful life-events Questionnaire. Psychiatric conditions were evaluated using the Structured Clinical Interview for Diagnostic and Statistical Manual of mental disorders. A total of 166 (80% females; mean age 44.7) patients completed the follow-up at 2 months after the detoxification program: of these 118 (71%) (78% females; mean age 44.7) stopped overuse and reverted to an episodic pattern of headache (Group A); 19 (11%) (89% females; mean age 41.3) kept overusing and maintained a chronic pattern of headache (Group B); and 29 (18%) (79% females; mean age 46.9) stopped overuse without any benefit on headache frequency (Group C). At the multivariate analyses, a higher number of early life emotional distress (Odds Ratio 11.096; = 0.037) arose as a prognostic factor for the outcome in Group B, while major depression during life-time (Odds Ratio 3.703; = 0.006) and higher number of severe stressful episodes in the past 10 years (Odds Ratio 1.679; = 0.045) were prognostic factors for the outcome of Group C. Data suggest that early life traumas and stressful events have a negative impact on the outcome of the detoxification program in subjects overusing acute medication for headache. The history of emotional childhood traumas is associated to the failure to cease overuse, whereas recent very serious life events are associated to the persistence of headache chronicity.
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http://dx.doi.org/10.3389/fneur.2019.00173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416203PMC
March 2019

The Effects of Transcutaneous Spinal Direct Current Stimulation on Neuropathic Pain in Multiple Sclerosis: Clinical and Neurophysiological Assessment.

Front Hum Neurosci 2019 12;13:31. Epub 2019 Feb 12.

Neurorehabilitation Unit, Department of Neurology, IRCCS C. Mondino Foundation, Pavia, Italy.

: Central neuropathic pain represents one of the most common symptoms in multiple sclerosis (MS) and it seriously affects quality of life. Spinal mechanisms may contribute to the pathogenesis of neuropathic pain in MS. Converging evidence from animal models and neurophysiological and clinical studies in humans suggests a potential effect of transcranial direct current stimulation (tc-DCS) on neuropathic pain. Spinal application of DCS, i.e., transcutaneous spinal DCS (ts-DCS), may modulate nociception through inhibition of spinal reflexes. Therefore, ts-DCS could represents an effective, safe and well-tolerated treatment for neuropathic pain in MS, a largely unexplored topic. This study is a pilot randomized double-blind sham-controlled trial to evaluate the efficacy of ts-DCS on central neuropathic pain in MS patients. : Thirty-three MS patients with central neuropathic pain were enrolled and randomly assigned to two groups in a double-blind sham-controlled design: anodal ts-DCS group ( = 19, 10 daily 20-min sessions, 2 mA) or sham ts-DCS group ( = 14, 10 daily 20-min sessions, 0 mA). The following clinical outcomes were evaluated before ts-DCS treatment (T0), after 10 days of treatment (T1) and 1 month after the end of treatment (T2): neuropathic pain symptoms inventory (NPSI), Ashworth Scale (AS) for spasticity and Fatigue Severity Scale (FSS). A subgroup of patients treated with anodal ts-DCS ( = 12) and sham ts-DCS ( = 11) also underwent a parallel neurophysiological study of the nociceptive withdrawal reflex (NWR) and the NWR temporal summation threshold (TST), two objective markers of pain processing at spinal level. : Anodal ts-DCS group showed a significant improvement in NPSI at T1, which persisted at T2, while we did not detect any significant change in AS and FSS. Sham ts-DCS group did not show any significant change in clinical scales. We observed a non-significant trend towards an inhibition of NWR responses in the anodal ts-DCS group at T1 and T2 when compared to baseline. : Anodal ts-DCS seems to have an early and persisting (i.e., 1 month after treatment) clinical efficacy on central neuropathic pain in MS patients, probably through modulation of spinal nociception. www.ClinicalTrials.gov, identifier #NCT02331654.
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http://dx.doi.org/10.3389/fnhum.2019.00031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379270PMC
February 2019

Body Weight Support Combined With Treadmill in the Rehabilitation of Parkinsonian Gait: A Review of Literature and New Data From a Controlled Study.

Front Neurol 2018 8;9:1066. Epub 2019 Feb 8.

Neurorehabilitation Unit and Parkinson Unit, IRCCS Mondino Foundation, Pavia, Italy.

Gait disorders represent disabling symptoms in Parkinson's Disease (PD). The effectiveness of rehabilitation treatment with Body Weight Support Treadmill Training (BWSTT) has been demonstrated in patients with stroke and spinal cord injuries, but limited data is available in PD. The aim of the study is to investigate the efficacy of BWSTT in the rehabilitation of gait in PD patients. Thirty-six PD inpatients were enrolled and performed rehabilitation treatment for 4-weeks, with daily sessions. Subjects were randomly divided into two groups: both groups underwent daily 40-min sessions of traditional physiokinesitherapy followed by 20-min sessions of overground gait training (Control group) or BWSTT (BWSTT group). The efficacy of BWSTT was evaluated with clinical scales and Computerized Gait Analysis (CGA). Patients were tested at baseline (T0) and at the end of the 4-weeks rehabilitation period (T1). Both BWSTT and Control groups experienced a significant improvement in clinical scales as FIM and UPDRS and in gait parameters for both interventions. Even if we failed to detect any statistically significant differences between groups in the different clinical and gait parameters, the intragroup analysis captured a specific pattern of qualitative improvement associated to cadence and stride duration for the BWSTT group and to the swing/stance ratio for the Control group. Four patients with chronic pain or anxious symptoms did not tolerate BWSTT. BWSTT and traditional rehabilitation treatment are both effective in improving clinical motor functions and kinematic gait parameters. BWSTT may represent an option in PD patients with specific symptoms that limit traditional overground gait training, e.g., severe postural instability, balance disorder, orthostatic hypotension. BWSTT is generally well-tolerated, though caution is needed in subjects with chronic pain or with anxious symptoms. www.ClinicalTrials.gov, identifier: NCT03815409.
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http://dx.doi.org/10.3389/fneur.2018.01066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375880PMC
February 2019

Nitroglycerin as a comparative experimental model of migraine pain: From animal to human and back.

Prog Neurobiol 2019 06 13;177:15-32. Epub 2019 Feb 13.

Headache Science Center, IRCCS C. Mondino Foundation, Pavia, Italy; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy. Electronic address:

Migraine is a disease for which there is still no defined pathophysiological etiology and few translational models. The organic nitrate nitroglycerin has been in use as an experimental model of migraine in both human and animal studies for several years. The drug produces a number of effects within the head, that includes blood vessels, nerves and brain areas that may produce a response similar to a migraine attack in predisposed subjects. A better understanding of the nature of these changes and how well they parallel a true migraine attack would allow for a translational model to better understand some of the mechanisms involved in the generation of a migraine attack. The present review summarizes the known body of knowledge of nitroglycerin effects evaluated in humans and animals as it relates to potential mechanisms associated with migraine headaches.
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http://dx.doi.org/10.1016/j.pneurobio.2019.02.002DOI Listing
June 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.
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http://dx.doi.org/10.1186/s10194-019-0966-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734365PMC
February 2019

Getting closer to a cure for migraine.

Nat Rev Neurol 2019 02;15(2):64-65

Headache Science Center, IRCCS Mondino Foundation, Pavia, Italy.

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http://dx.doi.org/10.1038/s41582-019-0134-zDOI Listing
February 2019

Dissecting out migraine complexity through comprehensive analysis of allodynia.

Brain 2019 01;142(1):5-8

Headache Science Centre, IRCCS Mondino Foundation, Pavia, Italy.

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http://dx.doi.org/10.1093/brain/awy315DOI Listing
January 2019
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