Publications by authors named "Xavier Moisset"

30 Publications

  • Page 1 of 1

Untreated patients with multiple sclerosis: a study of French expert centers.

Eur J Neurol 2021 Mar 1. Epub 2021 Mar 1.

Université Clermont Auvergne, CHU de Clermont-Ferrand, Inserm, Neuro-Dol, F-63000, Clermont-Ferrand, France.

Background: Disease modifying therapies (DMTs), have an impact on relapses and disease progression. Nonetheless, many patients with multiple sclerosis (pwMS) remain untreated. The objective of the present study was to determine the proportion of untreated patients with multiple sclerosis (pwMS) followed in expert centers in France and determine the predictive factors of non-treatment.

Methods: Retrospective cohort study. Data were extracted from the 38 centers participating in the European Database for Multiple Sclerosis (EDMUS) on 12/15/2018 and pwMS seen at least once during the study period (from June 15, 2016 to June 14, 2017) were included. Results Among the 21,189 pwMS (age 47.1±13.1; EDSS 3.4±2.4), 6,631 (31.3%; 95%CI=30.7-31.9) of the patients were not receiving any DMT. Although patients with a relapsing-remitting course (n = 11,693) were the most likely to receive DMT, 14.8% (95%CI = 14.2-15.4) were still untreated (6.8% never treated). After multivariate analysis among relapsing-remitting pwMS, the main factors explaining never having been treated were not having ≥9 lesions on brain MRI (OR = 0.52 [0.44-0.61]) and lower EDSS (OR = 0.78 [0.74-0.82]). Most patients with progressive MS (50.4% for secondary and 64.2% for primary progressive MS) did not receive any DMT during the study period, 11.6% for secondary and 34.0% for primary progressive MS had never received any DMT.

Conclusion: A significant proportion of pwMS did not receive any DMT, even though such treatments are reimbursed by the healthcare system for French patients. This result highlights the unmet need for current DMTs for a large subgroup of pwMS.
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http://dx.doi.org/10.1111/ene.14790DOI Listing
March 2021

Characteristics of pain in patients with pituitary adenomas: A cross-sectional study.

Eur J Pain 2021 Jan 5. Epub 2021 Jan 5.

Université Clermont Auvergne, CHU Clermont-Ferrand, Inserm, Neuro-Dol, Clermont-Ferrand, France.

Background: This study determines the prevalence and particularities of headache and pain with neuropathic characteristics (NC) in a large French group of patients with pituitary adenoma (PA).

Methods: Analysis of validated self-administered questionnaires, radiological characteristics and treatment strategies of PA was performed.

Results: Of the 221 sent questionnaires, 146 could be used for statistical analysis, 50% of which were completed by women. Among responders, 58.9% had pain: 30.1% migraine, 15.7% pain with NC and 13.1% other types of pain. Migraine was more common in patients with PA than in the general population (30.1% vs. 21.3%, p = .010) and attacks received appropriate treatment for less than 20% of these patients. Furthermore, the prevalence of chronic migraine was much higher than in the general population (6.8% vs. 2.2%, p = .003). Neuropathic pain was also more frequent in PA patients than in the general population (15.8% vs. 6.9%, p < .001). Neuropathic pain was most often located in the extremities and was frequently described as an 'electric shock', 'numbness', or 'pins-and-needles'. Multivariate analyses linked migraine to younger age, anxiety, pain with NC, and a visible tumour on MRI, regardless of its invasiveness or secretory nature.

Conclusions: Migraine headaches and neuropathic pain are more frequent and disabling in PA patients than in the general population. Both types of pain are comorbid in PA patients and are poorly treated. Migraine is associated with the presence of a tumour. Thus, biological mechanisms of this relationship need to be characterized to design optimal treatments for these individuals.

Significance: Migraine headaches and neuropathic pain are more common in PA patients than in the general population and are generally poorly treated. A systematic screening for migraine should be done by physicians in daily practice to provide adequate therapeutics.
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http://dx.doi.org/10.1002/ejp.1721DOI Listing
January 2021

Nasopharyngeal swab-induced pain for SARS-CoV-2 screening: A randomised controlled trial of conventional and self-swabbing.

Eur J Pain 2021 Jan 4. Epub 2021 Jan 4.

Université Clermont Auvergne, CHU de Clermont-Ferrand, Inserm, Clermont-Ferrand, France.

Background: Massive screening campaigns for SARS-CoV-2 are currently carried out throughout the world, relying on reverse-transcriptase-polymerase chain reaction (RT-PCR) following nasopharyngeal swabbing performed by a healthcare professional. Yet, due to the apprehension of pain induced by nasopharyngeal probing, poor adhesion to those screening campaigns can be observed. To enhance voluntary participation and to avoid unnecessary exposition to SARS-CoV-2, self-swabbing could be proposed. To date, no data have been published concerning pain induced by conventional- or self-swabbing. Thus, the primary objective of the present study was to evaluate pain induced with the conventional swabbing method and compare it to self-swabbing. Secondary objectives focused on swabbing-induced discomfort and acceptability of the two methods.

Methods: The study was conducted in Clermont-Ferrand medical school (France). Overall, 190 students were randomised into two groups and experienced either self- or conventional-swabbing. Each subject had to rate pain, discomfort and acceptability of such swabbing on a 0-10 numeric rating scale.

Results: No significant difference was found between the two methods. The mean pain level was 2.5 ± 1.9, 28% rating pain as ≥4/10. Discomfort was 4.8 ± 2.2, 66% indicating significant (≥4/10) discomfort. Higher pain and discomfort were associated with female sex. Acceptability was ≥8/10 for 89.0% of the subjects and all would have accepted to undergo a new test with the same technique if necessary.

Conclusion: Both conventional and self-swabbing induce low levels of pain for most young healthy volunteers whereas discomfort is very frequent. Nonetheless, both methods are indifferently well-accepted in medical students. Future studies amongst symptomatic subjects are awaited.

Significance: Using the thinnest available swabs, procedural pain induced by nasopharyngeal swabbing for SARS-CoV-2 screening is very low for most subjects and should not limit voluntary participation in screening campaigns. Self-swabbing does not lead to more pain or discomfort compared to conventional swabbing, is well-accepted, and could be proposed to optimize screening campaigns, at least in healthcare professionals.
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http://dx.doi.org/10.1002/ejp.1722DOI Listing
January 2021

Pharmacological treatment of central neuropathic pain: consensus of the Brazilian Academy of Neurology.

Arq Neuropsiquiatr 2020 14;78(11):741-752. Epub 2020 Dec 14.

Universidade de São Paulo, Faculdade de Medicina, Centro de Dor, Departamento de Neurologia, São Paulo SP, Brazil.

Background: Central neuropathic pain (CNP) is often refractory to available therapeutic strategies and there are few evidence-based treatment options. Many patients with neuropathic pain are not diagnosed or treated properly. Thus, consensus-based recommendations, adapted to the available drugs in the country, are necessary to guide clinical decisions.

Objective: To develop recommendations for the treatment of CNP in Brazil.

Methods: Systematic review, meta-analysis, and specialists opinions considering efficacy, adverse events profile, cost, and drug availability in public health.

Results: Forty-four studies on CNP treatment were found, 20 were included in the qualitative analysis, and 15 in the quantitative analysis. Medications were classified as first-, second-, and third-line treatment based on systematic review, meta-analysis, and expert opinion. As first-line treatment, gabapentin, duloxetine, and tricyclic antidepressants were included. As second-line, venlafaxine, pregabalin for CND secondary to spinal cord injury, lamotrigine for CNP after stroke, and, in association with first-line drugs, weak opioids, in particular tramadol. For refractory patients, strong opioids (methadone and oxycodone), cannabidiol/delta-9-tetrahydrocannabinol, were classified as third-line of treatment, in combination with first or second-line drugs and, for central nervous system (CNS) in multiple sclerosis, dronabinol.

Conclusions: Studies that address the treatment of CNS are scarce and heterogeneous, and a significant part of the recommendations is based on experts opinions. The CNP approach must be individualized, taking into account the availability of medication, the profile of adverse effects, including addiction risk, and patients' comorbidities.
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http://dx.doi.org/10.1590/0004-282X20200166DOI Listing
December 2020

Neuromodulation techniques for acute and preventive migraine treatment: a systematic review and meta-analysis of randomized controlled trials.

J Headache Pain 2020 Dec 10;21(1):142. Epub 2020 Dec 10.

Emergency Headache Center (Centre d'Urgences Céphalées), Department of Neurology, Lariboisière Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France.

Background: Several neuromodulation methods exists for migraine treatment. The aim of the present study was to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) focusing on migraine treatment using neurostimulation methods.

Methods: We searched Medline and Embase up to July 1, 2020 for RCTs reporting acute or preventive treatment of migraine with either non-invasive or invasive neurostimulation methods. Two researchers independently assessed the eligibility of the retrieved studies and extracted data. Outcomes for the quantitative synthesis were 2 h pain free for acute treatment and headache days per month for preventive treatment. We performed subgroup analyses by treatment (stimulation method and site of application). Estimates were pooled using random-effects meta-analysis.

Results: Thirty-eight articles were included in the qualitative analysis (7 acute, 31 preventive) and 34 in the quantitative evaluation (6 acute, 28 preventive). Remote electrical neuromodulation (REN) was effective for acute treatment. Data were insufficient to draw conclusions for any other techniques (single studies). Invasive occipital nerve stimulation (ONS) was effective for migraine prevention, with a large effect size but considerable heterogeneity, whereas supra-orbital transcutaneous electrical nerve stimulation (TENS), percutaneous electrical nerve stimulation (PENS), and high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) were effective, with small to medium effect sizes. Vagus-nerve stimulation, left prefrontal cortex rTMS, and cathodal transcranial direct current stimulation (tDCS) over the M1 had no significant effect and heterogeneity was high.

Conclusion: Several neuromodulation methods are of potential interest for migraine management, but the quality of the evidence is very poor. Future large and well-conducted studies are needed and could improve on the present results.
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http://dx.doi.org/10.1186/s10194-020-01204-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726868PMC
December 2020

Ketamine-Magnesium for Refractory Chronic Cluster Headache: A Case Series.

Headache 2020 Nov 31;60(10):2537-2543. Epub 2020 Oct 31.

Service de Neurologie, Université Clermont Auvergne, CHU de Clermont-Ferrand, Inserm, Clermont-Ferrand, France.

Objectives: To evaluate the safety and efficacy of ketamine-magnesium combination to reduce attacks in a series of patients with refractory chronic cluster headache (rCCH).

Background: Refractory chronic cluster headache (CCH) is a rare but highly debilitating condition that needs new treatment options. A previous publication reported that a single infusion of ketamine-magnesium combination was effective in 2 patients with rCCH.

Methods: The treatment was proposed to consecutive patients with rCCH seen in 2 French hospitals between November 2015 and February 2020 and who were resistant to at least 3 preventive treatments. They received a single ketamine infusion (0.5 mg/kg over 2 hours) combined with magnesium sulfate (3000 mg). The main outcome was a comparison of the number of daily attacks 2 weeks prior to the ketamine-magnesium infusion and 1 week after (on days 7 and 8). The second outcome was the percentage of responders (patients with ≥50% reduction in the frequency of daily attacks). Safety was assessed by the recording of adverse events during infusion. Descriptive statistics are presented as mean ± standard deviation.

Results: Seventeen patients (14 men), with an age of 35.2 ± 8.1 years, were included. They presented with CCH for 6.6 ± 4.3 years. The number of daily attacks decreased from 4.3 ± 2.4 before treatment to 1.3 ± 1.0 after treatment (difference: -3.1 (95% CI: -4.5 to -1.6), P < .001). Seventy six percent (13/17) were responders. Transient and mild sedation was reported by 7/17 patients (41.2%).

Conclusions: The ketamine-magnesium combination seems an effective and well-tolerated therapy for rCCH. Placebo-controlled studies should be conducted to further confirm these findings.
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http://dx.doi.org/10.1111/head.14005DOI Listing
November 2020

Relapses in Patients Treated with High-Dose Biotin for Progressive Multiple Sclerosis.

Neurotherapeutics 2020 Sep 22. Epub 2020 Sep 22.

CHU de Clermont-Ferrand, F-63000, Clermont-Ferrand, France.

High-dose biotin (HDB) is a therapy used in non-active progressive multiple sclerosis (PMS). Several reports have suggested that HDB treatment may be associated with an increased risk of relapse. We aimed to determine whether HDB increases the risk of clinical relapse in PMS and describe the characteristics of the patients who experience it. We conducted a French, multicenter, retrospective study, comparing a group of PMS patients treated with HDB to a matched control group. Poisson regression was applied to model the specific statistical distribution of the annualized relapse rate (ARR). A propensity score (PS), based on the inverse probability of treatment weighting (IPTW), was used to adjust for indication bias and included the following variables: gender, primary PMS or not, age, EDSS, time since the last relapse, and co-prescription of a DMT. Two thousand six hundred twenty-eight patients treated with HDB and 654 controls were analyzed with a follow-up of 17 ± 8 months. Among them, 148 validated relapses were observed in the group treated with biotin and 38 in the control group (p = 0.62). After adjustment based on the PS, the ARR was 0.044 ± 0.23 for the biotin-treated group and 0.028 ± 0.16 for the control group (p = 0.18). The more relapses there were before biotin, the higher the risk of relapse during treatment, independently from the use of HDB. While the number of relapses reported for patients with no previous inflammatory activity receiving biotin has gradually increased, the present retrospective study is adequately powered to exclude an elevated risk of relapse for patients with PMS treated with HDB.
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http://dx.doi.org/10.1007/s13311-020-00926-2DOI Listing
September 2020

Pregabalin: a better neuropathic pain treatment in rodents than in humans.

Pain 2020 10;161(10):2425-2427

Inserm U987, APHP, CHU Ambroise Paré Hospital, UVSQ, Paris-Saclay University, Boulogne-Billancourt, France.

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http://dx.doi.org/10.1097/j.pain.0000000000001993DOI Listing
October 2020

High Prevalence of Headaches During Covid-19 Infection: A Retrospective Cohort Study.

Headache 2020 11 5;60(10):2578-2582. Epub 2020 Aug 5.

CHU Clermont-Ferrand, Inserm, Neuro-Dol, CNRS 6023 Laboratoire Microorganismes: Génome Environnement (LMGE), Université Clermont Auvergne, Clermont-Ferrand, France.

Objectives: To document the prevalence of new headaches in patients with Covid-19 infection and the potential association with other neuro-sensorial symptoms (anosmia and ageusia). The persistence of these symptoms 1 month after recovery was also documented.

Background: Headaches are a very common symptom of viral infections. Surprisingly, early Chinese studies reported a relatively low prevalence (12-15%) of headaches associated with Covid-19.

Methods: All the patients with laboratory-confirmed or chest-CT-confirmed Covid-19 infection, diagnosed between February 27 and April 15 , 2020 in the dedicated laboratory of Clermont-Ferrand University Hospital were followed for 1 month after recovery.

Results: A total of 139 consecutive patients (mean [SD] age, 48.5 [15.3] years; 87 women [62.6%]) were interviewed 1 month after disappearance of fever and dyspnea (semi-structured phone interview). Overall, 59.0% (82/139) of people with Covid-19 had mild disease, 36.7% (51/139) had severe disease, and 4.3% (6/139) had critical illness. Eighty-two (59.0%; 95% CI: 50.3 to 67.3) reported new headaches during the acute phase and 3.6% (5/139) had persistent headaches 1 month after fever and dyspnea remission. Anosmia and ageusia were also very common, occurring in 60.4% (84/139) and 58.3% (81/139) of the patients, respectively. These 2 symptoms persisted in 14.4% (20/139) and 11.5% (16/139) of Covid-19 patients 1 month after recovery. Headaches were neither clearly associated with anosmia, nor with ageusia, and were not associated with disease severity (ie, requiring hospitalization or intensive care unit).

Conclusion: This specific study highlights the high prevalence of new headaches during Covid-19 infection in French patients. Further studies are needed to refine the characterization of patients with Covid-19-associated headaches.
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http://dx.doi.org/10.1111/head.13923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436456PMC
November 2020

Prevalence of Migraine and Neuropathic Pain in Rheumatic Diseases.

J Clin Med 2020 Jun 17;9(6). Epub 2020 Jun 17.

Neurology Department, Université Clermont Auvergne, CHU de Clermont-Ferrand, Inserm, Neuro-Dol, F-63000 Clermont Ferrand, France.

To investigate the physiopathology of pain in chronic inflammatory rheumatic diseases (CIRDs), we assessed the prevalence of migraine and neuropathic pain in 499 patients with CIRDs. We studied 238 patients with rheumatoid arthritis, 188 with spondyloarthritis (SpA), 72 with psoriatic arthritis (PsA), and 1 unclassified. Migraine was diagnosed according to IHS migraine diagnostic criteria. Neuropathic pain was diagnosed when patients scored at least 3 on the DN4 questionnaire. Participants completed a validated self-assessment questionnaire. Migraine prevalence was 34% (165/484), and it was highest in PsA. Risk factors for migraine were a high level of anxiety, female sex, young age, and TNF-alpha inhibitor treatment (OR = 1.90 (1.13-3.25)). Besides, high disease activity was a risk factor in SpA. Blood CRP level was not significantly associated with migraine. Of 493 patients with CIRDs, 21.5% had chronic pain with neuropathic characteristics. Compared to the French general population, these patients had significantly higher prevalences of migraine (two-fold) and neuropathic pain (three-fold). This study showed that migraine and neuropathic pain frequently occurred in patients with rheumatic diseases. Therefore, upon reporting residual pain, these patients should be checked for the presence of migraine or neuropathic pain, despite adequate clinical control of rheumatic disease.
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http://dx.doi.org/10.3390/jcm9061890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356241PMC
June 2020

Progressive Multifocal Leukoencephalopathy Incidence and Risk Stratification Among Natalizumab Users in France.

JAMA Neurol 2020 01;77(1):94-102

CHU de Nantes, Service de Neurologie, CIC015 INSERM, Nantes, France.

Importance: Risk of developing progressive multifocal leukoencephalopathy (PML) is the major barrier to using natalizumab for patients with multiple sclerosis (MS). To date, the association of risk stratification with PML incidence has not been evaluated.

Objective: To describe the temporal evolution of PML incidence in France before and after introduction of risk minimization recommendations in 2013.

Design, Setting, And Participants: This observational study used data in the MS registry OFSEP (Observatoire Français de la Sclérose en Plaques) collected between April 15, 2007, and December 31, 2016, by participating MS expert centers and MS-dedicated networks of neurologists in France. Patients with an MS diagnosis according to current criteria, regardless of age, were eligible, and those exposed to at least 1 natalizumab infusion (n = 6318) were included in the at-risk population. A questionnaire was sent to all centers, asking for a description of their practice regarding PML risk stratification. Data were analyzed in July 2018.

Exposures: Time from the first natalizumab infusion to the occurrence of PML, natalizumab discontinuation plus 6 months, or the last clinical evaluation.

Main Outcomes And Measures: Incidence was the number of PML cases reported relative to the person-years exposed to natalizumab. A Poisson regression model for the 2007 to 2016 period estimated the annual variation in incidence and incidence rate ratio (IRR), adjusted for sex and age at treatment initiation and stratified by period (2007-2013 and 2013-2016).

Results: In total, 6318 patients were exposed to natalizumab during the study period, of whom 4682 (74.1%) were female, with a mean (SD [range]) age at MS onset of 28.5 (9.1 [1.1-72.4]) years; 45 confirmed incident cases of PML were diagnosed in 22 414 person-years of exposure. The crude incidence rate for the whole 2007 to 2016 period was 2.00 (95% CI, 1.46-2.69) per 1000 patient-years. Incidence significantly increased by 45.3% (IRR, 1.45; 95% CI, 1.15-1.83; P = .001) each year before 2013 and decreased by 23.0% (IRR, 0.77; 95% CI, 0.61-0.97; P = .03) each year from 2013 to 2016.

Conclusions And Relevance: The results of this study suggest, for the first time, a decrease in natalizumab-associated PML incidence since 2013 in France that may be associated with a generalized use of John Cunningham virus serologic test results; this finding appears to support the continuation and reinforcement of educational activities and risk-minimization strategies in the management of disease-modifying therapies for multiple sclerosis.
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http://dx.doi.org/10.1001/jamaneurol.2019.2670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724170PMC
January 2020

Whole-body reversible neuropathic pain associated with right parieto-temporal operculum single inflammatory lesion in a patient with multiple sclerosis: A case report.

Eur J Pain 2019 11 22;23(10):1763-1766. Epub 2019 Aug 22.

CHU de Clermont-Ferrand, Clermont-Ferrand, France.

Background: The posterior insula and the medial parietal operculum (PIMO) are part of the pain network. Pain can be induced by direct stimulation of the PIMO, but the clinical consequence of lesions in this brain area is not well known.

Case Report: We report the case of a patient with multiple sclerosis who presented a relapse characterized by isolated widespread neuropathic pain. The MRI displayed a single new inflammatory lesion in the juxta cortical white matter of the opercular region. This lesion was extended to the parietal operculum and was associated with the pain syndrome. The patient was treated with high-dose intravenous methylprednisolone, and the pain disappeared progressively. Diffusion-tensor MRI showed that some of the fibres passing through the lesion ended in the PIMO.

Conclusion: Based on diffusion-tensor MRI we hypothesize that the partial disconnection from afference to the PIMO can lead to widespread neuropathic pain.

Significance: Most of the data concerning the functional role of the PIMO come from stereoelectroencephalography in presurgical evaluation of epilepsy, or from functional imaging (PET or fMRI). There is, however, very few data on the consequences of the lesion of the PIMO. Here, we report the first case of a transient widespread pain syndrome associated to a single, small and reversible inflammatory lesion of the PIMO. Thus, this case highlights the key role of the PIMO in spatial perception of pain.
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http://dx.doi.org/10.1002/ejp.1464DOI Listing
November 2019

Specific lumbar puncture training during clinical clerkship durably increases atraumatic needle use.

PLoS One 2019 10;14(6):e0218004. Epub 2019 Jun 10.

Service de Neurologie, CHU de Clermont-Ferrand, Université Clermont Auvergne, Clermont-Ferrand, France.

Background: Atraumatic needles are proposed to lower complication rates after lumbar puncture (LP). Only a minority of physicians use such needles. Here we aimed to assess the impact of specific training in LP during clinical clerkship on the proportion of medical students using atraumatic needles.

Methods: We performed a case-control study comparing medical students undergoing clinical clerkship and students undergoing specific LP training. The 176 students of a class underwent training in LP just before beginning their clinical rotations. This training consisted of 45 minutes of theoretical training and a 90-minute practical session with a dummy. Twenty students were selected from the class at random, and their competence was assessed with a multiple choice questionnaire (MCQ) and an objective structured clinical examination (OSCE), nine months after the specific training. These 20 cases were compared with 20 students randomly selected from a class of 180 students who had not undergone specific training in LP and were at the end of their clinical clerkship.

Results: We found that 60% of the students with specific training and 25% of those with classic clinical training used an atraumatic needle during the OSCE (p = 0.025). The mean MCQ (/100) scores obtained were 57±15 and 60±15 for the specific and classic training groups, respectively (p = 0.35). Overall OSCE score was similar in the two groups (63.5±9.3 vs. 65.8±9.3; p = 0.20).

Conclusion: Very few practicing physicians use atraumatic needles, which limits the teaching of their use to medical students. Specific training durably increases the use of appropriate needles.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218004PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557568PMC
March 2020

How to diagnose parkinsonian central pain?

Parkinsonism Relat Disord 2019 07 1;64:50-53. Epub 2019 May 1.

Department of Clinical Pharmacology and Neurosciences, Centre d'Investigation Clinique CIC1436, NS-Park/FCRIN Network, UMR ToNIC 1214, University Hospital of Toulouse, INSERM, University of Toulouse 3, Toulouse, France.

Among the different types of pain observed in Parkinson's disease, parkinsonian central pain (PCP) has the highest severity, and is poorly characterized and difficult to describe not only by patients but also by neurologists. Thus PCP remains not strictly defined and is difficult to distinguish from other types of pain on the basis of clinical description. Yet, standardizing PCP diagnosis is critical to improve the treatment of this debilitating pain subtype, but also to homogenize further studies investigating the pathophysiological mechanisms underlying this condition. Accounting for the lack of reliable validated positive clinical criteria for PCP, and as the clinical features of PCP are difficult to specify, we suggest to consider so far the gold standard diagnosis of PCP mainly based on exclusion criteria. We propose a new algorithm aiming to disentangle PCP from other chronic pain subtypes in Parkinson's disease, by sequentially ruling out what PCP is not.
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http://dx.doi.org/10.1016/j.parkreldis.2019.04.025DOI Listing
July 2019

Repetitive Transcranial Magnetic Stimulation Therapy (rTMS) for Endometriosis Patients with Refractory Pelvic Chronic Pain: A Pilot Study.

J Clin Med 2019 Apr 13;8(4). Epub 2019 Apr 13.

Department of Gynecological Surgery, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France.

Endometriosis concerns more than 10% of women of reproductive age, frequently leading to chronic pelvic pain. Repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) induces an analgesic effect. This effect on chronic pelvic pain is yet to be evaluated. The objective of this study was to assess the feasibility and effect of rTMS to reduce pain and improve quality of life (QoL) in patients with chronic pelvic pain due to endometriosis. This pilot, open-labelled prospective trial examined treatment by neuronavigated rTMS over M1, one session per day for 5 consecutive days. Each session consisted of 1.500 pulses at 10 Hz. We assessed tolerance, pain change and QoL until 4 weeks post treatment with a primary endpoint at day 8. Twelve women were included. No patients experienced serious adverse effects or a significant increase in pain. Nine women reported improvement on the Patient Global Impression of Change with a reduction in both pain intensity and pain interference (5.1 ± 1.4 vs. 4.1 ± 1.6, = 0.01 and 6.2 ± 2.1 vs. 4.2 ± 1.5, = 0.004, respectively). rTMS appears well tolerated and might be of interest for patients suffering from chronic pelvic pain for whom other treatments have failed. A randomized controlled trial is mandatory before proposing such treatment.
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http://dx.doi.org/10.3390/jcm8040508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518231PMC
April 2019

Dimethyl fumarate induced migrating polyarthralgias.

Joint Bone Spine 2019 05 3;86(3):399-400. Epub 2018 Aug 3.

CHU Gabriel-Montpied, 58, rue Montalembert, 63000 Clermont-Ferrand, France.

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http://dx.doi.org/10.1016/j.jbspin.2018.07.006DOI Listing
May 2019

Decreased prevalence of cancer in patients with multiple sclerosis: A case-control study.

PLoS One 2017 27;12(11):e0188120. Epub 2017 Nov 27.

Université Clermont-Auvergne, INSERM, Neuro-Dol, CHU Clermont-Ferrand, Service de Neurologie Clermont-Ferrand, France.

Background: Studies of cancer prevalence have produced conflicting results concerning the relative risk of overall and specific sub-types of cancer in patients with multiple sclerosis (MS). Contemporary controls and information on tobacco use and alcohol consumption are generally missing from previous studies.

Objectives: To evaluate lifetime cancer prevalence in a large cohort of MS patients relative to appropriate controls.

Methods: We conducted a case-control study, using a postal survey of a cohort of MS patients. Of the 1574 questionnaires sent, 1107 could be used for statistical analysis. Data from 1568 controls were prospectively collected using the same self-administered survey among consecutive out-patients in a single neurology department. Propensity scores matched on age, gender, and history of smoking and alcohol consumption were calculated.

Results: Among the MS patients, 7.32% had ever presented with a cancer, whereas 12,63% of the controls had, leading to a bootstrap matched odds ratio (OR) of 0.63; 95% CI 0.57-0.70. Although only exploratory, the use of DMT (immunomodulators or immunosupressants) did not appear to increase this risk (p = 0.42). The disease course also did not affect cancer prevalence.

Conclusion: MS was associated with a reduced overall cancer risk.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188120PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703510PMC
December 2017

Improvement of quality of life and its relationship with neuropsychiatric outcomes in patients with multiple sclerosis starting treatment with natalizumab: A 3-year follow-up multicentric study.

J Neurol Sci 2017 11 6;382:148-154. Epub 2017 Oct 6.

Service de Neurologie, CHU de Clermont-Ferrand, Université Clermont Auvergne, F-63000 Clermont-Ferrand, France; Neuro-Dol, Inserm U1107, Université Clermont Auvergne, F-63000 Clermont-Ferrand, France.

Background: Health-related quality of life (HRQoL) is impaired in multiple sclerosis (MS) but can be improved by disease-modifying therapies such as natalizumab. However, the predictive factors and neuropsychiatric correlates of HRQoL improvement are unknown.

Methods: In this study, 48 patients with relapsing-remitting MS were included in a 3-year open-label, single group, multicenter, clinical trial (NCT01392872). HRQoL was measured by the disease-specific MusiQoL questionnaire, together with physical disability, cognition, fatigue, anxiety and depression scores at baseline, 6months, 12months, 18months and 36months after starting natalizumab therapy.

Results: Compared to baseline, global HRQoL, as measured with the index of the MusiQoL, was significantly increased 6months after the beginning of natalizumab therapy, with medium effect-size (58.6±16.2 vs 69.8±18.9, p<0.001, Cohen's d=0.63). This improvement was maintained over time for up to 3years and mainly concerned activity of daily living, psychological well-being, symptoms and coping (p<0.001 for every dimensions). The variation of global HRQoL after 3years was negatively correlated with the variation of fatigue score (r=-0.44, p=0.015). Furthermore, a higher fatigue score at baseline was correlated with improvement in global HRQoL 3years afterwards (r=0.34, p=0.041), independently of age, educational level, disease duration and disability at baseline (β=2.45, p=0.020). Disability at baseline, cognitive impairment, anxiety and depression failed to predict or correlate with global HRQoL improvement in multivariate analyses.

Conclusion: Natalizumab improved HRQoL quickly and sustainably in patients with relapsing-remitting MS. In terms of HRQoL, natalizumab seems to benefit mostly patients with more marked fatigue at baseline.
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http://dx.doi.org/10.1016/j.jns.2017.10.008DOI Listing
November 2017

Ketamine Infusion Combined With Magnesium as a Therapy for Intractable Chronic Cluster Headache: Report of Two Cases.

Headache 2017 Sep 3;57(8):1261-1264. Epub 2017 Jul 3.

CHU Clermont-Ferrand, Centre d'Evaluation et de Traitement de la Douleur, Clermont, Ferrand, France.

Background: Chronic cluster headache (CH) is a rare, highly disabling primary headache condition. As NMDA receptors are possibly overactive in CH, NMDA receptor antagonists, such as ketamine, could be of interest in patients with intractable CH.

Case Reports: Two Caucasian males, 28 and 45 years-old, with chronic intractable CH, received a single ketamine infusion (0.5 mg/kg over 2 h) combined with magnesium sulfate (3000 mg over 30 min) in an outpatient setting. This treatment led to a complete relief from symptoms (attack frequency and pain intensity) for one patient and partial relief (50%) for the other patient, for 6 weeks in both cases.

Conclusion: The NMDA receptor is a potential target for the treatment of chronic CH. Randomized, placebo-controlled studies are warranted to establish both safety and efficacy of such treatment.
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http://dx.doi.org/10.1111/head.13135DOI Listing
September 2017

Co-occurrence of Pain Symptoms and Somatosensory Sensitivity in Burning Mouth Syndrome: A Systematic Review.

PLoS One 2016;11(9):e0163449. Epub 2016 Sep 22.

Clermont Université, Université d'Auvergne, Neuro-Dol, Clermont-Ferrand & Inserm U1107, Clermont-Ferrand, France.

Background: Burning mouth syndrome (BMS) is a chronic and spontaneous oral pain with burning quality in the tongue or other oral mucosa without any identifiable oral lesion or laboratory finding. Pathogenesis and etiology of BMS are still unknown. However, BMS has been associated with other chronic pain syndromes including other idiopathic orofacial pain, the dynias group and the family of central sensitivity syndromes. This would imply that BMS shares common mechanisms with other cephalic and/or extracephalic chronic pains. The primary aim of this systematic review was to determine whether BMS is actually associated with other pain syndromes, and to analyze cephalic and extracephalic somatosensory sensitivity in these patients.

Methods: This report followed the PRISMA Statement. An electronic search was performed until January 2015 in PubMed, Cochrane library, Wiley and ScienceDirect. Searched terms included "burning mouth syndrome OR stomatodynia OR glossodynia OR burning tongue OR oral burning". Studies were selected according to predefined inclusion criteria (report of an association between BMS and other pain(s) symptoms or of cutaneous cephalic and/or extracephalic quantitative sensory testing in BMS patients), and a descriptive analysis conducted.

Results: The search retrieved 1512 reports. Out of these, twelve articles met criteria for co-occurring pain symptoms and nine studies for quantitative sensory testing (QST) in BMS patients. The analysis reveals that in BMS patients co-occurring pain symptoms are rare, assessed by only 0.8% (12 of 1512) of the retrieved studies. BMS was associated with headaches, TMD, atypical facial pain, trigeminal neuralgia, post-herpetic facial pain, back pain, fibromyalgia, joint pain, abdominal pain, rectal pain or vulvodynia. However, the prevalence of pain symptoms in BMS patients is not different from that in the age-matched general population. QST studies reveal no or inconsistent evidence of abnormal cutaneous cephalic and extracephalic somatosensory sensitivity.

Conclusions: There is no evidence for a high rate of other pain symptoms or somatosensory impairments co-occurring with BMS. These results thus suggest that BMS rather depends on specific mechanisms, likely at the trigeminal level. Nevertheless, more thoroughly conducted research is required to draw definitive conclusion.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033415PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0163449PLOS
September 2016

Who Performs Lumbar Puncture, How Many Do They Perform, How and Why? A Retrospective Study of 6,594 Cases.

Eur Neurol 2016 24;76(1-2):8-11. Epub 2016 Jun 24.

Clermont Universitx00E9;, Universitx00E9; d'Auvergne, Neuro-Dol, Inserm U1107, Clermont-Ferrand, France.

Background: The number and indications of lumbar punctures (LPs) performed nowadays are unknown. The primary aim of this work was to report the number of LPs performed in each of the departments of 2 French university hospitals, their indications and the prevalence of atraumatic spinal needles used.

Methods: We carried out a retrospective study of all the LPs performed in 2014. The clinical department in which the intervention was performed and the final diagnosis was made from the Medical Information Department. The type of needles (cutting or atraumatic) used during the study period was also available.

Results: In 2014, 6,594 LPs were performed. Overall, 80% were performed for diagnostic purposes. Twenty percent of these LPs were performed in the Neurology Department and were usually carried out at routine check-ups. Overall, atraumatic needles were used in 8.0% of cases. Overall, 1.4 LPs per 100 hospital stays were performed and 0.8 LP for 100 Emergency department admissions.

Conclusion: LP is a routine procedure for many clinicians and although neurologists perform the largest number of LPs, they are doing only one fifth of all procedures. Atraumatic needles are underused.
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http://dx.doi.org/10.1159/000447452DOI Listing
September 2017

[Use of strong opioids in chronic non-cancer pain in adults. Evidence-based recommendations from the French Society for the Study and Treatment of Pain].

Presse Med 2016 Apr 7;45(4 Pt 1):447-62. Epub 2016 Apr 7.

AP-HP, hôpital Raymond-Poincaré, université de Versailles-St-Quentin, service d'anesthésie réanimation chirurgicale, 104, boulevard Raymond-Poincaré, 92380 Garches, France. Electronic address:

Objectives: An urgent need is to improve the efficacy and safety of use of strong opioids in chronic non-cancer pain (CNCP) through responsible prescription rules supported by scientific evidence.

Methods: Clinical questions addressing the indication, the benefice, the risk and the precautions were formulated. A task force composed of physicians from several medical specialties involved in managing CNCP was charged to elaborate evidence-based recommendations. A systematic literature search was performed using CENTRAL, MEDLINE and EMBASE databases. The approach of the Grading of Recommendations Assessment, Development and Evaluation was applied to evaluate outcomes.

Results: We selected 21 meta-analyses and 31 cohort studies for analysis. Fifteen recommendations are provided. Strong opioids are not recommended in fibromyalgia and primary headaches. Strong opioids have been shown to be moderately effective against CNCP due to osteoarthritis of the lower limbs, and for back pain and neuropathic pain. Their introduction is advised only after the failure of first-line treatments, combined with patient care, provided that the patient is made aware of the advantages and risks. It is not advisable to continue strong opioids treatment for longer than three months if no improvement in pain, function or quality of life is observed. It is also recommended not to prescribe doses exceeding 150mg/day morphine equivalent. Misuse risk factors should be investigated before prescription and misuse should be assessed at each renewal. Priority should be given to extended-release forms. It is recommended not to use transmucosal rapid-release forms of fentanyl for the management of CNCP.

Conclusion: These recommendations are intended for all doctors needing to prescribe strong opioids in CNCP.
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http://dx.doi.org/10.1016/j.lpm.2016.02.014DOI Listing
April 2016

Is there pain with neuropathic characteristics in patients with amyotrophic lateral sclerosis? A cross-sectional study.

Palliat Med 2016 May 12;30(5):486-94. Epub 2015 Aug 12.

Neuro-Dol, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France Centre SLA, Service de Neurologie, CHU Clermont-Ferrand, Clermont-Ferrand, France

Background: Amyotrophic lateral sclerosis is a progressive debilitating and lethal disorder, characterized by degeneration of motor neurons that warrant palliative care. Pain is frequent in patients with amyotrophic lateral sclerosis and significantly impacts on quality of life.

Aim: To describe pain and assess the prevalence of pain with neuropathic characteristics in patients with amyotrophic lateral sclerosis.

Design: Cross-sectional survey from March 2009 to October 2013.

Setting/participants: Amyotrophic lateral sclerosis patients underwent multidisciplinary assessment and completed questionnaires measuring the severity and impact of pain and anxiety. The Douleur Neuropathique-4 questionnaire was used to look for pain with neuropathic characteristics.

Results: Of 96 clinical evaluations, 93 were usable for analysis (age at onset: 62 ± 12.5 years; disease duration: 34 ± 33 months). The overall pain prevalence was 66%, with 9% experiencing pain with neuropathic characteristics. Pain was most often located in the neck and shoulders (38% of pain patients). Neck and shoulder pain was associated with neck (p = 0.04) and proximal upper limb muscular weakness (p = 0.02), respectively. Pain was not associated with disease duration, respiratory or nutritional parameters, but with higher anxiety scores (p = 0.01). Patients with neuropathic characteristics pain did not differ significantly from patients with or without pain, except that they had higher minimal pain intensity score (p < 0.05). Neuropathic characteristics pain was frequently spontaneous (rarely evoked) and described as numbness, burning, electric shock, tingling, and pins-and-needle.

Conclusion: Even if amyotrophic lateral sclerosis is a disease of the motor system, pain is frequent and can rarely have neuropathic characteristics. Pain must be always sought and appropriately treated to limit quality of life impairment.
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http://dx.doi.org/10.1177/0269216315600332DOI Listing
May 2016

Prolonged continuous theta-burst stimulation is more analgesic than 'classical' high frequency repetitive transcranial magnetic stimulation.

Brain Stimul 2015 Jan-Feb;8(1):135-41. Epub 2014 Oct 18.

INSERM U-987, Centre d'Evaluation et de Traitement de la Douleur, CHU Ambroise Paré, Assistance Publique Hôpitaux de Paris, F-92100 Boulogne Billancourt, France; Université Versailles-Saint-Quentin, Versailles F-78035, France.

Background: Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) at high frequency (>5 Hz) induces analgesic effects, probably by activating pain modulation systems. A new rTMS paradigm--theta burst stimulation (TBS)--consists of bursts of three pulses at 50 Hz repeated five times per second. Like high frequency rTMS, both intermittent and prolonged continuous TBS (iTBS and pcTBS) lead to a facilitation of cortical excitability.

Objectives: (1) to evaluate the analgesic effects of neuronavigated iTBS and pcTBS, comparing them with those of classical high frequency rTMS (10 Hz) over the left M1, (2) to elucidate the role of conditioned pain modulation (CPM) in the antinociceptive effect of rTMS and (3) to investigate possible correlations between analgesia and cortical excitability.

Methods: Fourteen healthy volunteers participated in four experimental sessions, carried out in a random order (iTBS, pcTBS, 10 Hz rTMS or sham). Cold pain threshold, CPM and cortical excitability measurements were carried out before and after rTMS.

Results: We found that the analgesic effects of 10 Hz rTMS and pcTBS were significantly superior to those of sham rTMS. Moreover, pcTBS was significantly more effective than 10 Hz rTMS (P = 0.026). Analgesia did not seem to be driven by changes in CPM or cortical excitability.

Conclusion: Prolonged cTBS has considerable clinical potential, as it has a shorter treatment duration (by a factor 8) and stronger analgesic effects than the classical high frequency protocol. Studies in patients are required to confirm the potential of this new stimulation paradigm for clinical applications.
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http://dx.doi.org/10.1016/j.brs.2014.10.006DOI Listing
May 2015

Severe bilateral amyotrophic neuralgia associated with major dysphagia secondary to acute hepatitis E.

F1000Res 2013 26;2:259. Epub 2013 Nov 26.

CHU Clermont-Ferrand, Service de Neurologie, CHU Gabriel Montpied, Clermont-Ferrand, F-63000, France ; Neuro-Dol, Inserm U1107, Douleur Trigéminale et Migraine, Faculté de Chirurgie Dentaire, F-63000, F-63000, France ; Clermont Université, Université d'Auvergne, Clermont-Ferrand, F-63000, France.

Introduction: Several acute neurological syndromes can be triggered by immune events. Hepatitis E virus (HEV), an emerging infectious disease, can be one of these triggers.

Case Report: We report the case of a 36-year-old man that presented nausea and a dull abdominal pain for a week and then felt an acute neuralgic pain involving both shoulders that lasted for 8 to 10 hours. Immediately after, the patient presented a severe bilateral muscular weakness of the proximal part of both upper limbs, corresponding to an amyotrophic neuralgia. Two days after the shoulder pain, the patient presented a dysphagia necessitating tube feeding.  A blood sample confirmed hepatitis caused by hepatitis E virus (HEV; genotype 3F). Oral feeding resumed progressively after five months. The patient was fully independent for the activities of daily living but was still unable to work after six months.

Conclusion: Amyotrophic neuralgia and hepatitis E are both under-diagnosed. It is noteworthy that HEV can trigger amyotrophic neuralgia. Antiviral drugs, oral steroids and intravenous immunoglobulins can be proposed, but the optimal treatment has  not yet been determined.
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http://dx.doi.org/10.12688/f1000research.2-259.v2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886787PMC
February 2014

Migraine headaches and pain with neuropathic characteristics: comorbid conditions in patients with multiple sclerosis.

Pain 2013 Dec 2;154(12):2691-2699. Epub 2013 Aug 2.

Clermont Université, Université d'Auvergne, Neuro-Dol;Inserm U1107, Douleur Trigéminale et Migraine, Faculté de chirurgie dentaire, Clermont-Ferrand F-63000, France Clermont Université, Université d'Auvergne, CHU Clermont-Ferrand, Service de Neurologie, CHU Gabriel Montpied, Clermont-Ferrand F-63000, France Clermont Université, Université d'Auvergne, CHU Clermont-Ferrand, Service de Biostatistiques, CHU Gabriel Montpied, Clermont-Ferrand F-63000, France Clermont Université, Université d'Auvergne, UMR 6284 UdA-CNRS, ISIT, Science de l'Image pour Techniques Interventionnelles, Clermont-Ferrand F-63000, France Clermont Université, Université d'Auvergne, CHU Clermont-Ferrand, Service d'Odontologie, CHU Estaing, Clermont-Ferrand F-63000, France.

We conducted a postal survey to assess the prevalence and characteristics of neuropathic pain and migraine in a cohort of multiple sclerosis (MS) patients. Of the 1300 questionnaires sent, 673 could be used for statistical analysis. Among the respondents, the overall pain prevalence in the previous month was 79%, with 51% experiencing pain with neuropathic characteristics (NCs) and 46% migraine. MS patients with both migraine and NC pain (32% of the respondents) reported more severe pain and had lower health-related quality of life than MS patients with either migraine or NC pain. Pain intensity in MS patients with migraine was moderate (6.0 ± 0.1). Migraine was mostly episodic, but headaches were occurring on ≥15 days per month in 15% of those with migraine. MS patients with migraine were younger and had shorter disease durations than those with NC pain. NC pain was most often located in the extremities, back and head, and was frequently described as tingling and pins-and-needles. The intensity of NC pain was low to moderate (4.9 ± 0.1), but positively correlated with the number of painful body sites. Nonetheless, patients with NC pain were more disabled (with a higher Expanded Disability Status Scale and pain interference index) than patients with migraine. Migraine, but not NC pain, was associated with age, disease duration, relapsing-remitting course, and interferon-beta treatment. This suggests that NC pain and migraine are mediated by different mechanisms. Therefore, pain mechanisms that specifically operate in MS patients need to be characterized to design optimal treatments for these individuals.
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http://dx.doi.org/10.1016/j.pain.2013.07.050DOI Listing
December 2013

Functional brain imaging of trigeminal neuralgia.

Eur J Pain 2011 Feb 6;15(2):124-31. Epub 2010 Jul 6.

INSERM U-987, Physiopathologie et Pharmacologie Clinique de la Douleur, Hôpital Ambroise Paré, Boulogne-Billancourt F-92100, France.

We used functional magnetic resonance imaging (fMRI) to analyze changes in brain activity associated with stimulation of the cutaneous trigger zone in patients with classic trigeminal neuralgia (CTN). Fifteen consecutive patients with CTN in the second or third division of the nerve, were included in this study. The fMRI paradigm consisted of light tactile stimuli of the trigger zone and the homologous contralateral area. Stimulation of the affected side induced pain in seven patients, but was not painful in eight patients on the day of the experiment. Painful stimuli were associated with significantly increased activity in the spinal trigeminal nucleus (SpV), thalamus, primary and secondary somatosensory cortices (S1, S2), anterior cingulate cortex (ACC), insula, premotor/motor cortex, prefrontal areas, putamen, hippocampus and brainstem. Nonpainful stimulation of the trigger zone activated all but three of these structures (SpV, brainstem and ACC). After a successful surgical treatment, activation induced by stimulation of the operated side was confined to S1 and S2. Our data demonstrate the pathological hyperexcitability of the trigeminal nociceptive system, including the second order trigeminal sensory neurons during evoked attacks of CTN. Such sensitization may depend on pain modulatory systems involving both the brainstem (i.e. periaqueductal gray and adjacent structures) and interconnected cortical structures (i.e. ACC). The fact that large portions of the classical 'pain neuromatrix' were also activated during nonpainful stimulation of the trigger zone, could reflect a state of maintained sensitization of the trigeminal nociceptive systems in CTN.
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http://dx.doi.org/10.1016/j.ejpain.2010.06.006DOI Listing
February 2011

Anatomical connections between brain areas activated during rectal distension in healthy volunteers: a visceral pain network.

Eur J Pain 2010 Feb 26;14(2):142-8. Epub 2009 May 26.

INSERM U792, Physiopathologie et pharmacologie clinique de la douleur, Hôpital Ambroise Paré, 92100 Boulogne, France.

Diffusion Tensor Imaging (DTI) is a promising new imaging method allowing in vivo mapping of anatomical connections in the living human brain. We combined DTI with functional magnetic resonance imaging (fMRI) to investigate the anatomical relationships between areas involved in visceral sensations in humans. Non-painful and moderately painful rectal distensions were performed in 11 healthy women (38.4+/-3.1years). fMRI was used to analyse the changes in brain activity during both types of distension. Then, DTI was applied for tracking fibers between the main activated regions. Non-painful distension bilaterally activated the PreFrontal Cortex (PFC), the Anterior Cingulate Cortex (ACC) and the right insula. Painful distension bilaterally activated the primary (S1) and secondary (S2) somatosensory cortices, the motor cortex, the frontal inferior gyrus, the thalamus, the insula, the striatum and the cerebellum. DTI revealed direct connections between insula, and the four areas more frequently activated in this study, i.e. ACC, thalamus, S1, S2 and PFC. The combined use of fMRI and DTI in healthy subjects during rectal distension revealed a neural network of visceral sensory perception involving the insula, thalamus, somatosensory cortices, ACC and PFC.
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http://dx.doi.org/10.1016/j.ejpain.2009.04.011DOI Listing
February 2010

Glycine inhibitory dysfunction induces a selectively dynamic, morphine-resistant, and neurokinin 1 receptor- independent mechanical allodynia.

J Neurosci 2009 Feb;29(8):2519-27

INSERM, U929, F-63000 Clermont-Ferrand, France.

Dynamic mechanical allodynia is a widespread and intractable symptom of neuropathic pain for which there is a lack of effective therapy. We recently provided a novel perspective on the mechanisms of this symptom by showing that a simple switch in trigeminal glycine synaptic inhibition can turn touch into pain by unmasking innocuous input to superficial dorsal horn nociceptive specific neurons through a local excitatory, NMDA-dependent neural circuit involving neurons expressing the gamma isoform of protein kinase C. Here, we further investigated the clinical relevance and processing of glycine disinhibition. First, we showed that glycine disinhibition with strychnine selectively induced dynamic but not static mechanical allodynia. The induced allodynia was resistant to morphine. Second, morphine did not prevent the activation of the neural circuit underlying allodynia as shown by study of Fos expression and extracellular-signal regulated kinase phosphorylation in dorsal horn neurons. Third, in contrast to intradermal capsaicin injections, light, dynamic mechanical stimuli applied under disinhibition did not produce neurokinin 1 (NK1) receptor internalization in dorsal horn neurons. Finally, light, dynamic mechanical stimuli applied under disinhibition induced Fos expression only in neurons that did not express NK1 receptor. To summarize, the selectivity and morphine resistance of the glycine-disinhibition paradigm adequately reflect the clinical characteristics of dynamic mechanical allodynia. The present findings thus reveal the involvement of a selective dorsal horn circuit in dynamic mechanical allodynia, which operates through superficial lamina nociceptive-specific neurons that do not bear NK1 receptor and provide an explanation for the differences in the pharmacological sensitivity of neuropathic pain symptoms.
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http://dx.doi.org/10.1523/JNEUROSCI.3923-08.2009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6666240PMC
February 2009

Brain imaging of neuropathic pain.

Neuroimage 2007 10;37 Suppl 1:S80-8. Epub 2007 Apr 10.

INSERM U-792, Centre de Traitement et d'Evaluation de la Douleur, CHU Ambroise Pare, 9, avenue Charles de Gaulle, 92100 Boulogne-Billancourt cedex, France.

Many studies have focused on defining the network of brain structures involved in normal physiological pain. The different dimensions of pain perception (i.e., sensory discriminative, affective/emotional, cognitive/evaluative) have been shown to depend on different areas of the brain. In contrast, much less is known about the neural basis of pathological chronic pain. In particular, it is unclear whether such pain results from changes to the physiological "pain matrix". We review here studies on changes in brain activity associated with neuropathic pain syndromes-a specific category of chronic pain associated with peripheral or central neurological lesions. Patients may report combinations of spontaneous pain and allodynia/hyperalgesia-abnormal pain evoked by stimuli that normally induce no/little sensation of pain. Modern neuroimaging methods (positron emission tomography (PET) and functional MRI (fMRI)) have been used to determine whether different neuropathic pain symptoms involve similar brain structures and whether these structures are related to the physiological "pain matrix". PET studies have suggested that spontaneous neuropathic pain is associated principally with changes in thalamic activity and the medial pain system, which is preferentially involved in the emotional dimension of pain. Both PET and fMRI have been used to investigate the basis of allodynia. The results obtained have been very variable, probably reflecting the heterogeneity of patients in terms of etiology, lesion topography, symptoms and stimulation procedures. Overall, these studies indicated that acute physiological pain and neuropathic pain have distinct although overlapping brain activation pattern, but that there is no unique "pain matrix" or "allodynia network".
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http://dx.doi.org/10.1016/j.neuroimage.2007.03.054DOI Listing
October 2007