Discordance between pain specialists and patients on the perception of dependence on pain medication: A multi-centre cross-sectional study.

AIM: Patients with chronic non-cancer pain are referred to pain centres to improve their pain treatment. The discontinuation of pain medications in case of poor efficacy can be difficult to accept for patients, particularly opioid analgesics. Previous research has described that from the patients' perspective, the psychological relief of a negative effect of chronic pain and withdrawal symptoms of prescription opioids represent drivers of persistent use and first stage of opioid use disorder, despite insufficient pain relief. There is no validated tool to investigate this psychological dependence. This study aimed to assess discordance between patients and pain specialists in their perception of dependence on pain medication and investigate associations with characteristics of patients, type of pain and iatrogenic pharmacodependence. METHODS: Self-administered questionnaires (patients and physicians) were administered in six pain centres in France. A question on perceived dependence on pain medications was addressed to the patient and the physician in a matched pair. Discordance between them was evaluated by the Cohen kappa coefficient. Demographics, pain, anxiety and depression, pain medication withdrawal symptoms, diverted use, and craving represented variables studied in a multivariate model as potentially associated with patient-physician discordance. RESULTS: According to the 212 pairs of completed questionnaires, a perceived dependence was reported by the majority of patients (65.6%) and physicians (68.4%). However, the concordance was fair (kappa=0.38; CI [95%]: 0.25-0.51). Almost all patients (89.3%) were treated with an opioid analgesic. A higher likelihood of discordance was observed when patients suffered from nociplastic pain (odds ratio [OR]: 2.72, 95% [CI]: 1.29-5.84). CONCLUSION: Medical shared-decision for changing pain treatment could be improved by taking into account the perception of patient dependence on medications for pain relief and or psychoactive effects, particularly in nociplastic pain for which the treatment is challenging.

Somatotopy of the sensory thalamus: inputs from directional deep brain stimulation in pain patients.

OBJECTIVE: The sensory ventroposterior (VP) thalamic nuclei display a mediolateral somatotopic organization (respectively head, arm, and leg). We studied this somatotopy using directional VP deep brain stimulation (DBS) in patients treated for chronic neuropathic pain. METHODS: Six patients with central (four) or peripheral (two) neuropathic pain were treated by VP DBS using directional leads in a prospective study (clinicaltrials.gov NCT03399942). Lead-DBS toolbox was used for leads localization, visualization, and modeling of the volume of tissue activated (VTA). Stimulation was delivered in each direction, 1 month after surgery and correlated to the location of stimulation-induced paresthesias. The somatotopy was modeled by correlating the respective locations of paresthesias and VTAs. We recorded 48 distinct paresthesia maps corresponding to 48 VTAs (including 36 related to directional stimulation). RESULTS: We observed that, in each patient, respective body representations of the trunk, upper limb, lower limb, and head were closely located around the lead. These representations differed across patients, did not follow a common organization and were not concordant with the previously described somatotopic organization of the sensory thalamus. INTERPRETATION: Thalamic reorganization has been reported in chronic pain patients compared to non-pain patients operated for movement disorders in previous studies using intraoperative recordings and micro-stimulation. Using a different methodology, namely 3D representation of the VTA by the directional postoperative stimulation through a stationary electrode, our study brings additional arguments in favor of a reorganization of the VP thalamic somatotopy in patients suffering from chronic neuropathic pain of central or peripheral origin.

Triptan use in elderly over 65 years and the risk of hospitalization for serious vascular events.

BACKGROUND: Several studies have focused on the use of triptan and the risk of acute vascular events but the existence of such association is still debated and has never been quantified in patients over 65 years. To assess whether triptan use among older is associated with an increased risk of hospitalization for acute vascular events. METHODS: A propensity score-matched cohort study was designed using the French national health insurance database linked to hospital stays. Patients aged ≥ 65 years, newly treated by triptans between 2011 and 2014, were included… The primary event was hospitalization for an acute ischemic vascular event within de 90 days following triptan initiation. Association with triptan exposure was investigated through cox regression model, considering exposure at inclusion, and with exposure as a time-varying variable A case-crossover (CCO) and a self-controlled case series (SCCS) analyses were also conducted to address potential residual confounding. RESULTS: The cohort included 24, 774 triptan users and 99 096 propensity matched controls (mean (SD) age: 71 years (5.9), 74% of women). Within 90 days after cohort entry, 163 events were observed in the triptan group, and 523 in the control group (0.66% vs. 0.53%, adjusted hazard ratio (aHR) exposed/not exposed 1.25 95%CI [1.05-1.49]; aHR time-varying 8.74 [5.21-14.66]). The association was significant (CCO) for all events (adjusted odds ratio (aOR1.63 [1.22-2.19]) with a more consistent association with cerebral events (aOR 2.14 [1.26-3.63]). The relative incidence (RI) for all events was 2.13 [1.76-2.58] in the SCCS, for cardiac (RI: 1.67 [1.23-2.27]) and for cerebral events (RI: 3.20, [2.30-4.45]). CONCLUSION: The incidence of acute vascular events was low among triptan users. We found that triptan use among older may be associated with a low increased risk for acute vascular events, which may be more marked for cerebral events such as stroke, than for cardiac events.

Cyclic vomiting syndrome, a common language? A 20-year bibliometric study.

BACKGROUND: Cyclic vomiting syndrome (CVS) is recognized as an episodic syndrome associated with migraine in the last version of the International Classification of Headache Disorders (ICHD-3). It manifests as stereotypical episodes of intense nausea and vomiting, occurring preferentially in childhood. Over the last 2 decades, the knowledge of this disorder has increased. The diagnostic criteria have been modified, through the evolution of several successive classifications. Actually, two classifications are prominent in the literature: the ICHD-3 and the Rome IV classification. The predictable periodicity of episodes is only recognized in the ICHD-3. OBJECTIVE: We aimed to analyze the evolution of CVS literature in the last 2 decades, with a focus on CVS criteria used in these papers. METHODS: We conducted a bibliometric study. We searched in the Web of Science database all papers in English literature with the term CVS in the abstract or title, in the category "article" or "review", published from 2001 to 2020. We searched within the paper which classification was used or mentioned. RESULTS: In total, 213 papers were analyzed. 116 papers exclusively concerned childhood and adolescence CVS, or were written by pediatric practitioners. For most of the papers, the corresponding author was specialized in the field of gastroenterology. The Rome III classification was the main classification used or mentioned. The ICHD-3 and its beta version were mostly used or mentioned by the authors affiliated to the neurologic field. CONCLUSION: This study shows the growth in the number of publications on CVS. It highlights the lack of reference to the ICHD, in particular by practitioners in the field of gastroduodenal disorders. This should encourage the achievement of a common classification with the different scientific societies.

Occipital Nerve Stimulation for Recurrent Trigeminal Neuralgia Without Occipital Pain.

OBJECTIVES: Trigeminal neuralgia (TN) is a severe, debilitating pain condition causing physical and emotional distress. Although the management of TN is well codified with medical and then surgical treatments, 15% to 30% of patients will experience intractable pain. Neuromodulation techniques have been scarcely used for refractory TN, with only small case series and short-term follow-up. MATERIALS AND METHODS: We conducted a retrospective study of patients treated with occipital nerve stimulation (ONS) for medically and surgically resistant TN without painful trigeminal neuropathy. The effectiveness of the ONS was evaluated using the Barrow Neurological Institute (BNI) pain score and the pain relief (0%-100%) at best and at last follow-up. RESULTS: Seven patients who have refractory TN were included. The mean age at ONS was 49 years. The mean pain duration was 8.6 years. The mean number of medical and surgical treatments before ONS was six and five, respectively. A percutaneous trial was performed in five of seven patients; all responded (pain relief > 40%), and four of five patients experienced pain recurrence after explantation. Eventually, six patients had a permanent ONS implantation. The average BNI pain score before implantation was V. The mean follow-up after implantation was 59 months. All patients reported an improvement after implantation. The average BNI score and mean pain relief at best were IIIa and 86.7%, respectively. At last follow-up, the average BNI score and mean pain relief were IIIa and 58.0%, respectively, with three patients experiencing pain recurrence. Adverse events were reported for four patients who required surgical revision for lead breakage (1), erosion (1), migration (1), or hardware-related discomfort (1). One patient finally underwent explantation because of infection. CONCLUSIONS: Although ONS is not validated in this indication, these results suggest that it can induce an improvement in TN recurring after several surgical treatments, and the benefit of the stimulation can be sustained in the long term. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT01842763.

The teaching of headache medicine in France: A questionnaire-based study.

BACKGROUND: The treatment of patients with headache represents an important part of a neurologist's activity. It requires sufficient training for neurology residents. In France, residents in neurology can complete this training by attending specialized consultations or by participating in a postgraduate training program called "Diplôme Inter-Universitaire Migraine et Céphalées" (DIUMC). OBJECTIVE: The objective of this cross-sectional study was to investigate the French residents' knowledge in headache medicine and the impact of different types of training in headache medicine that are available in France. METHODS: An anonymous survey was carried out among 548 French residents in neurology. RESULTS: The questionnaires of 121 residents (22.1%) were analyzed. Among them, 54.5% (66/121) had no complementary training apart from the internship (Group 1), 21.5% (26/121) had attended only specialized consultations (Group 2), and 24% (29/121) had participated in the DIUMC (Group 3). There was no difference between all groups regarding the knowledge of the prevalence of primary or chronic headaches. There was almost no difference between the groups in the management of episodic migraine. In contrast, the management of tension-type headache and chronic headache was better known by residents of Group 3 than residents of Group 1. In these two diseases, residents of Group 3 offered prophylactic treatment more often. Almost 29% of the residents (35/121) had read the French guidelines for the diagnosis and management of migraine. In Group 3, residents had read them significantly more often (1.6% in Group 1, 38.5% in Group 2 and 62.1% in Group 3, p < 0.001). CONCLUSION: This study shows the lack of knowledge among French neurology residents regarding headache medicine. It highlights the interest of specific training programs that could improve the practical and theoretical knowledge of future neurologists.

Treatment of Chronic Refractory Pain by Combined Deep Brain Stimulation of the Anterior Cingulum and Sensory Thalamus (EMOPAIN Study): Rationale and Protocol of a Feasibility and Safety Study.

BACKGROUND: Deep Brain Stimulation (DBS) of the sensory thalamus has been proposed for 40 years to treat medically refractory neuropathic pain, but its efficacy remains partial and unpredictable. Recent pilot studies of DBS targeting the ACC, a brain region involved in the integration of the affective, emotional, and cognitive aspects of pain, may improve patients suffering from refractory chronic pain. ACC-DBS could be complementary to thalamic DBS to treat both the sensory-discriminative and the affective components of chronic pain, but the safety of combined DBS, especially on cognition and affects, has not been studied. METHODS: We propose a prospective, randomized, double-blind, and bicentric study to evaluate the feasibility and safety of bilateral ACC-DBS combined with unilateral thalamic DBS in adult patients suffering from chronic unilateral neuropathic pain, refractory to medical treatment. After a study period of six months, there is a cross-over randomized phase to compare the efficacy (evaluated by pain intensity and quality of life) and safety (evaluated by repeated neurological examination, psychiatric assessment, cognitive assessment, and assessment of affective functions) of combined ACC-thalamic DBS and thalamic DBS only, respectively. DISCUSSION: The EMOPAIN study will show if ACC-DBS is a safe and effective therapy for patients suffering from chronic unilateral neuropathic pain, refractory to medical treatment. The design of the study will, for the first time, assess the efficacy of ACC-DBS combined with thalamic DBS in a blinded way.

Hypnotherapy for irritable bowel syndrome: patient expectations and perceptions.

INTRODUCTION: Numerous studies have shown that hypnotherapy (HT) is effective in irritable bowel syndrome (IBS) using traditional symptom severity end points. However, there is now interest in capturing the patient's perception of their illness and treatment because what patients expect from their treatment may differ from that of their healthcare provider. OBJECTIVE: To record patient perceptions and expectations of hypnotherapy as well as their symptom response. METHODS: 150 consecutive IBS patients (116 females, 34 males, aged 16-81 years) receiving hypnotherapy completed questionnaires recording IBS symptom severity, quality of life, noncolonic symptoms, anxiety and depression levels before and after treatment. Their expectations and perceptions of HT were also recorded, including a free text reflection. RESULTS: 121 patients (81%) responded to treatment consistent with our previous experience. Symptom severity scores, noncolonic symptoms, quality of life, anxiety and depression significantly all improved after HT (p < 0.001). Expectancy of an improvement with hypnotherapy was greater in those who did not respond to treatment (63%) than those who did (57%, p < 0.001). Scepticism and apprehension were common before treatment and replaced with enthusiasm afterwards. Free text responses after treatment were overwhelmingly positive. Patients also reported a variety of other benefits and even 20 of 29 symptom nonresponders (70%) still considered treatment worthwhile. CONCLUSION: Although initially perceived negatively, hypnotherapy improved symptoms and resulted in a wide range of additional benefits. Expectation did not necessarily influence outcome. Recording IBS symptoms alone does not fully capture the patient's experience of treatment and needs to be considered in future research.

Hemiplegic Migraine Associated With PRRT2 Variations: A Clinical and Genetic Study.

BACKGROUND AND OBJECTIVE: PRRT2 variants have been reported in a few cases of patients with hemiplegic migraine. To clarify the role of PRRT2 in familial hemiplegic migraine, we studied this gene in a large cohort of affected probands. METHODS: PRRT2 was analyzed in 860 probands with hemiplegic migraine, and PRRT2 variations were identified in 30 probands. Genotyping of relatives identified a total of 49 persons with variations whose clinical manifestations were detailed. RESULTS: PRRT2 variations were found in 12 of 163 probands who previously tested negative for CACNA1A, ATP1A2, and SCN1A variations and in 18 of 697 consecutive probands screened simultaneously on the 4 genes. In this second group, pathogenic variants were found in 105 individuals, mostly in ATP1A2 (42%), followed by CACNA1A (26%), PRRT2 (17%), and SCN1A (15%). The PRRT2 variations included 7 distinct variants, 5 of which have already been described in persons with paroxysmal kinesigenic dyskinesia and 2 new variants. Eight probands had a deletion of the whole PRRT2 gene. Among the 49 patients with variations in PRRT2, 26 had pure hemiplegic migraine and 16 had hemiplegic migraine associated with another manifestation: epilepsy (8), learning disabilities (5), hypersomnia (4), or abnormal movement (3). Three patients had epilepsy without migraine: 2 had paroxysmal kinesigenic dyskinesia without migraine, and 1 was asymptomatic. DISCUSSION: PRRT2 should be regarded as the fourth autosomal dominant gene for hemiplegic migraine and screened in any affected patient, together with the 3 other main genes. Further studies are needed to understand how the same loss-of-function PRRT2 variations can lead to a wide range of neurologic phenotypes, including paroxysmal movement disorder, epilepsy, learning disabilities, sleep disorder, and hemiplegic migraine.

Relevant factors for neurologists to define effectiveness of migraine preventive drugs and take decisions on treatment. My-LIFE European Delphi survey.

BACKGROUND: Clinical guidelines agree that preventive treatment should be considered in patients with uncontrolled migraine despite acute medications or patients with ≥4 migraine days per month. However, the criteria to define the effectiveness of treatment and the factors that inform the decision to (dis)continue it are not clearly defined in clinical practice. METHODS: Overall, 148 healthcare practitioners from five European countries completed a two-wave questionnaire. The Steering Committee defined a simulated set of 108 migraine patient profiles based on the combination of five factors (frequency of the attacks, intensity of the attacks, use of acute migraine medications, patient perception and presence/absence of tolerable side effects). These profiles were used in a Delphi survey among European neurologists to identify the criteria that should be used to decide treatment response and continuation using a conjoint analysis approach. RESULTS: Consensus was reached for 82/108 (76%) of profiles regarding treatment response, and for 86/108 (80%) regarding treatment continuation. Multivariable logistic regression analysis showed that a ≥50% reduction in the use of acute migraine medications and positive patient's perception of treatment were the most important factors that lead to the decision of continuing (combined factors, OR = 18.3, 95% CI 13.4-25.05). CONCLUSIONS: This survey identifies two relevant outcome measures: one objective (use of acute migraine treatment medications) and one subjective (positive patient perception) that guide the clinician decision to continue preventive treatment in migraine patients. SIGNIFICANCE: In clinical practice, criteria to define the effectiveness of migraine preventive treatment and factors that guide treatment stop or continuation are not clearly defined. In this simulated clinical setting study, a reduction in the use of acute migraine medications was the factor associated with preventive treatment effectiveness definition. This study also revealed that factors strongly associated with the decision of treatment continuation in real life are the acute migraine medications use and a positive patient's perception of treatment effectiveness.

Occipital Nerve Stimulation for Refractory Chronic Cluster Headache: A Cost-Effectiveness Study.

INTRODUCTION: Occipital nerve stimulation (ONS) is proposed to treat refractory chronic cluster headache (rCCH), but its cost-effectiveness has not been evaluated, limiting its diffusion and reimbursement. MATERIALS AND METHODS: We performed a before-and-after economic study, from data collected prospectively in a nation-wide registry. We compared the cost-effectiveness of ONS associated with conventional treatment (intervention and postintervention period) to conventional treatment alone (preintervention period) in the same patients. The analysis was conducted on 76 rCCH patients from the French healthcare perspective at three months, then one year by extrapolation. Because of the impact of the disease on patient activity, indirect cost, such as sick leave and disability leave, was assessed second. RESULTS: The average total cost for three months was €7602 higher for the ONS strategy compared to conventional strategy with a gain of 0.07 quality-adjusted life-years (QALY), the incremental cost-effectiveness ratio (ICER) was then €109,676/QALY gained. The average extrapolated total cost for one year was €1344 lower for the ONS strategy (p = 0.5444) with a gain of 0.28 QALY (p < 0.0001), the ICER was then €-4846/QALY gained. The scatter plot of the probabilistic bootstrapping had 80% of the replications in the bottom right-hand quadrant, indicating that the ONS strategy is dominant. The average indirect cost for three months was €377 lower for the ONS strategy (p = 0.1261). DISCUSSION: This ONS cost-effectiveness study highlighted the limitations of a short-time horizon in an economic study that may lead the healthcare authorities to reject an innovative strategy, which is actually cost-effective. One-year extrapolation was the proposed solution to obtain results on which healthcare authorities can base their decisions. CONCLUSION: Considering the burden of rCCH and the efficacy and safety of ONS, the demonstration that ONS is dominant should help its diffusion, validation, and reimbursement by health authorities in this severely disabled population.

The neurologist and the hydrops.

The presence of endolymphatic hydrops has been studied in many neurological disorders. The pathophysiological mechanisms may involve CSF pressure variations, transmitted to the innear ear. This hydrops could play a role in vestibular or cochlear symptoms. For the ENT specialist, the etiological diagnosis of endolymphatic hydrops is a challenge, and neurological etiologies must be known. The treatment of these neurological causes could be effective on cochleo-vestibular symptoms. The knowledge of endolymphatic hydrops could also be a target for noninvasive tests, able to estimate CSF pressure variations. For the neurologist, this could represent a useful tool for the diagnosis and follow-up, in some of these neurological disorders, related to a CSF pressure imbalance. The purpose of this paper is to summarize literature data on endolymphatic hydrops in neurological disorders. We define some neurological conditions, for which there is a particular interest in noninvasive investigations of endolymphatic hydrops.

Severe migraine and its control: A proposal for definitions and consequences for care.

Currently many patients with severe migraine do not receive appropriate treatment and are never referred to specialist headache centres. On the other hand, specialist headache centres are frequently attended by patients whose migraines could be managed adequately in the community. One reason for this may be the absence of standardised definitions of migraine severity and control and of a treatment algorithm for orientating difficult-to-treat patients to specialist headache centres. Based on a review of the relevant literature and consensus meetings, proposals have been made for these items. We propose that migraine should be considered severe if headache frequency is at least eight migraine days per month or, if headaches are less frequent, the HIT-6 score is ≥60 or ≥50% of headaches require complete interruption of activity. The proposed definition of migraine control is defined on the basis of appropriate response to acute headache therapy and to preventative therapy. A treatment algorithm is proposed to assess migraine control regularly and to adapt therapy accordingly. These proposals may contribute to developing and testing strategies for management of severe disease with appropriate and effective preventive treatment strategies. With the anticipated introduction of new possibilities for migraine prevention in the near future, the time is ripe for a holistic approach to migraine management.

A retrospective observation on 105 patients with chronic cluster headache receiving indomethacin.

BACKGROUND: Indomethacin (IMC) as a prophylactic treatment is considered to be ineffective in cluster headache (CH). However, small series suggested the interest of IMC in CH. Some authors support that an IMC test is useful in all trigeminal autonomic cephalalgias. We described clinical features of IMC responders in a retrospective cohort of chronic cluster headache (CCH). METHODS: This single-center and retrospective study was conducted in a tertiary care specialist headache center in France. Patients were selected between January 2007 and December 2008. We included all patients fulfilling CCH criteria (ICHD-3-beta). Data were collected from medical records. We recorded all the prescriptions of IMC as a prophylactic treatment. Responders were defined by 50% reduction in attack frequency; complete response was defined by disappearance of the attacks. The non-responders must have received at least 100 mg daily during 7 days. RESULTS: The study consisted of 324 CCH, 121 female (37%) and 203 males (63%) with an average age at onset of 33.93 (± 14.71) years. Of the patients, 105 were treated with IMC. Thirty patients (29%) were responders. Thirty-four patients (32%) were non-responders. Responding status was undefined for 41 patients (39%). Twelve patients (11%) had a complete response. Responders were composed by 18 women (60%) and 12 men (40%) and had on average 44.89 (± 12.88) years. The minimal effective dose was 86.11 mg daily (± 48.72). DISCUSSION: This study shows the interest of IMC in CCH patients. We recommend an IMC test as a third-line treatment in CCH.

Long-Term Efficacy of Occipital Nerve Stimulation for Medically Intractable Cluster Headache.

BACKGROUND: Occipital nerve stimulation (ONS) has been proposed to treat refractory chronic cluster headache (rCCH) but its efficacy has only been showed in small short-term series. OBJECTIVE: To evaluate ONS long-term efficacy in rCCH. METHODS: We studied 105 patients with rCCH, treated by ONS within a multicenter ONS prospective registry. Efficacy was evaluated by frequency, intensity of pain attacks, quality of life (QoL) EuroQol 5 dimensions (EQ5D), functional (Headache Impact Test-6, Migraine Disability Assessment) and emotional (Hospital Anxiety Depression Scale [HAD]) impacts, and medication consumption. RESULTS: At last follow-up (mean 43.8 mo), attack frequency was reduced >50% in 69% of the patients. Mean weekly attack frequency decreased from 22.5 at baseline to 9.9 (P < .001) after ONS. Preventive and abortive medications were significantly decreased. Functional impact, anxiety, and QoL significantly improved after ONS. In excellent responders (59% of the patients), attack frequency decreased by 80% and QoL (EQ5D visual analog scale) dramatically improved from 37.8/100 to 73.2/100. When comparing baseline and 1-yr and last follow-up outcomes, efficacy was sustained over time. In multivariable analysis, low preoperative HAD-depression score was correlated to a higher risk of ONS failure. During the follow-up, 67 patients experienced at least one complication, 29 requiring an additional surgery: infection (6%), lead migration (12%) or fracture (4.5%), hardware dysfunction (8.2%), and local pain (20%). CONCLUSION: Our results showed that long-term efficacy of ONS in CCH was maintained over time. In responders, ONS induced a major reduction of functional and emotional headache-related impacts and a dramatic improvement of QoL. These results obtained in real-life conditions support its use and dissemination in rCCH patients.