Deep brain stimulation in Latin America in comparison with the US and Europe in a real-world population: indications, demographics, techniques, technology, and adverse events.

OBJECTIVE: The aim of this study was to provide geographic comparisons of deep brain stimulation (DBS) procedures in Latin America with the US and Europe regarding primary indications, demographic information, clinical and device-related adverse events, technology used, and patient outcomes using the Medtronic Product Surveillance Registry data as of July 31, 2021. METHODS: Two thousand nine hundred twelve patients were enrolled in the registry (2782 received DBS and 1580 are currently active). Fourteen countries contributed 44,100 years of device experience to the registry. DBS centers in Latin America are located in Colombia (n = 3), Argentina (n = 1), Brazil (n = 1), and Mexico (n = 1). Fisher's exact test was used to compare the difference in proportions of categorical variables between regions. The Wilcoxon signed-rank test was used for the EQ-5D index score change from baseline to follow-up. RESULTS: The most common indication for DBS was Parkinson's disease across all regions. In Latin America, dystonia was the second most common indication, compared to essential tremor in other regions. There was a striking finding with respect to age-patients were an average of 10 years younger at DBS implantation in Latin America. This difference was most likely due to the greater number of patients with dystonia receiving the device implants. The intraoperative techniques were quite similar, showing the same level of quality and covering the main principles of the surgeries with some variations in the brand of frames, planning software, and microrecording systems. Rechargeable batteries were significantly more common in Latin America (72.37%) than in the US (6.44%) and Europe (9.9%). Staging of the DBS procedure differed, with only 11.84% in Latin America staging the procedure compared with 97.58% and 34.86% in the US and Europe, respectively. The EQ-5D score showed significant improvements in all regions during the first 6-12 months (p < 0.0001). However, the 24-month follow-up only showed an improvement in the scale for Latin America (p < 0.0001). CONCLUSIONS: DBS was performed in Latin America with similar indications, techniques, and technology as in the US and Europe. Important differences were found, with Latin America implementing more regular use of rechargeable devices, including younger patients at the time of surgery, and showing more sustained quality of life improvements at 24 months of follow-up. The authors hypothesize that these disparities stem from differences in resources among regions. However, more studies are needed to standardize DBS practice across the world to improve patients' quality of life and provide high-quality care.

Dissecting central post-stroke pain: a controlled symptom-psychophysical characterization.

Central post-stroke pain affects up to 12% of stroke survivors and is notoriously refractory to treatment. However, stroke patients often suffer from other types of pain of non-neuropathic nature (musculoskeletal, inflammatory, complex regional) and no head-to-head comparison of their respective clinical and somatosensory profiles has been performed so far. We compared 39 patients with definite central neuropathic post-stroke pain with two matched control groups: 32 patients with exclusively non-neuropathic pain developed after stroke and 31 stroke patients not complaining of pain. Patients underwent deep phenotyping via a comprehensive assessment including clinical exam, questionnaires and quantitative sensory testing to dissect central post-stroke pain from chronic pain in general and stroke. While central post-stroke pain was mostly located in the face and limbs, non-neuropathic pain was predominantly axial and located in neck, shoulders and knees (P < 0.05). Neuropathic Pain Symptom Inventory clusters burning (82.1%, n = 32, P < 0.001), tingling (66.7%, n = 26, P < 0.001) and evoked by cold (64.1%, n = 25, P < 0.001) occurred more frequently in central post-stroke pain. Hyperpathia, thermal and mechanical allodynia also occurred more commonly in this group (P < 0.001), which also presented higher levels of deafferentation (P < 0.012) with more asymmetric cold and warm detection thresholds compared with controls. In particular, cold hypoesthesia (considered when the threshold of the affected side was <41% of the contralateral threshold) odds ratio (OR) was 12 (95% CI: 3.8-41.6) for neuropathic pain. Additionally, cold detection threshold/warm detection threshold ratio correlated with the presence of neuropathic pain (ρ = -0.4, P < 0.001). Correlations were found between specific neuropathic pain symptom clusters and quantitative sensory testing: paroxysmal pain with cold (ρ = -0.4; P = 0.008) and heat pain thresholds (ρ = 0.5; P = 0.003), burning pain with mechanical detection (ρ = -0.4; P = 0.015) and mechanical pain thresholds (ρ = -0.4, P < 0.013), evoked pain with mechanical pain threshold (ρ = -0.3; P = 0.047). Logistic regression showed that the combination of cold hypoesthesia on quantitative sensory testing, the Neuropathic Pain Symptom Inventory, and the allodynia intensity on bedside examination explained 77% of the occurrence of neuropathic pain. These findings provide insights into the clinical-psychophysics relationships in central post-stroke pain and may assist more precise distinction of neuropathic from non-neuropathic post-stroke pain in clinical practice and in future trials.

Dissecting neuropathic from poststroke pain: the white matter within.

ABSTRACT: Poststroke pain (PSP) is a heterogeneous term encompassing both central neuropathic (ie, central poststroke pain [CPSP]) and nonneuropathic poststroke pain (CNNP) syndromes. Central poststroke pain is classically related to damage in the lateral brainstem, posterior thalamus, and parietoinsular areas, whereas the role of white matter connecting these structures is frequently ignored. In addition, the relationship between stroke topography and CNNP is not completely understood. In this study, we address these issues comparing stroke location in a CPSP group of 35 patients with 2 control groups: 27 patients with CNNP and 27 patients with stroke without pain. Brain MRI images were analyzed by 2 complementary approaches: an exploratory analysis using voxel-wise lesion symptom mapping, to detect significant voxels damaged in CPSP across the whole brain, and a hypothesis-driven, region of interest-based analysis, to replicate previously reported sites involved in CPSP. Odds ratio maps were also calculated to demonstrate the risk for CPSP in each damaged voxel. Our exploratory analysis showed that, besides known thalamic and parietoinsular areas, significant voxels carrying a high risk for CPSP were located in the white matter encompassing thalamoinsular connections (one-tailed threshold Z > 3.96, corrected P value <0.05, odds ratio = 39.7). These results show that the interruption of thalamocortical white matter connections is an important component of CPSP, which is in contrast with findings from nonneuropathic PSP and from strokes without pain. These data can aid in the selection of patients at risk to develop CPSP who could be candidates to pre-emptive or therapeutic interventions.

Neurological Impacts of Chronic Methylmercury Exposure in Munduruku Indigenous Adults: Somatosensory, Motor, and Cognitive Abnormalities.

There has been increasing evidence about mercury (Hg) contamination in traditional populations from the Amazon Basin due to illegal gold mining. The most concerning health impact is neurotoxicity caused by Hg in its organic form: methylmercury (MeHg). However, the severity and extent of the neurotoxic effects resulting from chronic environmental exposure to MeHg are still unclear. We conducted a clinical-epidemiological study to evaluate the neurological impacts of chronic MeHg exposure in Munduruku indigenous people, focusing on somatosensory, motor, and cognitive abnormalities. All participants were subjected to a systemized neurological exam protocol, including Brief Cognitive Screening Battery (BCSB), verbal fluency test, and Stick Design Test. After the examination, hair samples were collected to determine MeHg levels. Data collection took place between 29 October and 9 November 2019, in three villages (Sawré Muybu, Poxo Muybu, and Sawré Aboy) from Sawré Muybu Indigenous Land, Southwest of Pará state. One hundred and ten individuals >12 years old were included, 58 of which were men (52.7%), with an average age of 27.6 years (range from 12 to 72). Participants' median MeHg level was 7.4 µg/g (average: 8.7; S.D: 4.5; range: 2.0-22.8). In Sawré Aboy village, the median MeHg level was higher (12.5 µg/g) than in the others, showing a significant statistical exposure gradient (Kruskal-Wallis test with p-value < 0.001). Cerebellar ataxia was observed in two participants with MeHg levels of 11.68 and 15.68 µg/g. Individuals with MeHg exposure level ≥10 µg/g presented around two-fold higher chances of cognitive deficits (RP: 2.2; CI 95%: 1.13-4.26) in BCSB, and in the verbal fluency test (RP: 2.0; CI 95%: 1.18-3.35). Furthermore, adolescents of 12 to 19 years presented three-fold higher chances of verbal development deficits, according to the fluency test (RP: 3.2; CI 95%: 1.06-9.42), than individuals of 20 to 24 years. The worsened motor and cognitive functions are suggestive of neurotoxicity due to chronic MeHg exposure. In conclusion, we believe monitoring and follow-up measures are necessary for chronic mercury exposed vulnerable people, and a basic care protocol should be established for contaminated people in the Brazilian Unified Health System.

Mercury Exposure in Munduruku Indigenous Communities from Brazilian Amazon: Methodological Background and an Overview of the Principal Results.

The Amazonian indigenous peoples depend on natural resources to live, but human activities' growing impacts threaten their health and livelihoods. Our objectives were to present the principal results of an integrated and multidisciplinary analysis of the health parameters and assess the mercury (Hg) exposure levels in indigenous populations in the Brazilian Amazon. We carried out a cross-sectional study based on a census of three Munduruku indigenous villages (Sawré Muybu, Poxo Muybu, and Sawré Aboy), located in the Sawré Muybu Indigenous Land, between 29 October and 9 November 2019. The investigation included: (i) sociodemographic characterization of the participants; (ii) health assessment; (iii) genetic polymorphism analysis; (iv) hair mercury determination; and (v) fish mercury determination. We used the logistic regression model with conditional Prevalence Ratio (PR), with the respective 95% confidence intervals (CI95%) to explore factors associated with mercury exposure levels ≥6.0 µg/g. A total of 200 participants were interviewed. Mercury levels (197 hair samples) ranged from 1.4 to 23.9 µg/g, with significant differences between the villages (Kruskal-Wallis test: 19.9; p-value < 0.001). On average, the general prevalence of Hg exposure ≥ 6.0 µg/g was 57.9%. For participants ≥12 years old, the Hg exposure ≥6.0 µg/g showed associated with no regular income (PR: 1.3; CI95%: 1.0-1.8), high blood pressure (PR: 1.6; CI95%: 1.3-2.1) and was more prominent in Sawré Aboy village (PR: 1.8; CI95%: 1.3-2.3). For women of childbearing age, the Hg exposure ≥6.0 µg/g was associated with high blood pressure (PR: 1.9; CI95%: 1.2-2.3), with pregnancy (PR: 1.5; CI95%: 1.0-2.1) and was more prominent among residents in Poxo Muybu (PR: 1.9; CI95%: 1.0-3.4) and Sawré Aboy (PR: 2.5; CI95%: 1.4-4.4) villages. Our findings suggest that chronic mercury exposure causes harmful effects to the studied indigenous communities, especially considering vulnerable groups of the population, such as women of childbearing age. Lastly, we propose to stop the illegal mining in these areas and develop a risk management plan that aims to ensure the health, livelihoods, and human rights of the indigenous people from Amazon Basin.

Dry needling has lasting analgesic effect in shoulder pain: a double-blind, sham-controlled trial.

INTRODUCTION: Myofascial pain syndrome (MPS) affects most patients with chronic shoulder pain. Dry needling (DN) is a common treatment for MPS, but its temporal pattern and sensory effects remain unknown. OBJECTIVES: We evaluated in a randomized, sham-controlled study the pattern of analgesic efficacy and local sensory changes of a single session of DN for MPS in patients with chronic shoulder pain. METHODS: Patients with chronic shoulder pain were randomized into active (n = 20) or sham (n = 21) groups. A single DN was performed by a researcher blinded to group assignment and pain outcomes. Pain intensity was assessed by the numeric rating score, and sensory thresholds were evaluated with a quantitative sensory testing protocol, including the area of tactile sensory abnormalities 7 days before needling, right before, and 7 days after the intervention. RESULTS: Dry needling led to significant larger pain intensity reduction (from 6.30 ± 2.05 to 2.40 ± 2.45 in the active group; P = 0.02, effect size = -1.3 (95% CI [-2.0 to -0.68]); (number necessary to treat = 2.1). Pain reduction scores were significantly different on the second day after needling and persisted so until the seventh day and were accompanied by improvement in other dimensions of pain and a decrease in the area of mechanical hyperalgesia in the active DN group alone (P < 0.05). CONCLUSION: Active trigger points DN provided analgesic effects compared with sham and decreased the area of local mechanical hyperalgesia. These findings have practical clinical implications and may provide mechanistic insights behind MPS.

Posterior-superior insular deep transcranial magnetic stimulation alleviates peripheral neuropathic pain - A pilot double-blind, randomized cross-over study.

OBJECTIVES: Peripheral neuropathic pain (pNeP) is prevalent, and current treatments, including drugs and motor cortex repetitive transcranial magnetic stimulation (rTMS) leave a substantial proportion of patients with suboptimal pain relief. METHODS: We explored the intensity and short-term duration of the analgesic effects produced in pNeP patients by 5 days of neuronavigated deep rTMS targeting the posterior superior insula (PSI) with a double-cone coil in a sham-controlled randomized cross-over trial. RESULTS: Thirty-one pNeP patients received induction series of five active or sham consecutive sessions of daily deep-rTMS to the PSI in a randomized sequence, with a washout period of at least 21 days between series. The primary outcome [number of responders (>50% pain intensity reduction from baseline in a numerical rating scale ranging from 0 to 10)] was significantly higher after real (58.1%) compared to sham (19.4%) stimulation (p = 0.002). The number needed to treat was 2.6, and the effect size was 0.97 [95% CI (0.6; 1.3)]. One week after the 5th stimulation day, pain scores were no longer different between groups, and no difference in neuropathic pain characteristics and interference with daily living were present. No major side effects occurred, and milder adverse events (i.e., short-lived headaches after stimulation) were reported in both groups. Blinding was effective, and analgesic effects were not affected by sequence of the stimulation series (active-first or sham-first), age, sex or pain duration of participants. DISCUSSION: PSI deep-rTMS was safe in refractory pNeP and was able to provide significant pain intensity reduction after a five-day induction series of treatments. Post-hoc assessment of neuronavigation targeting confirmed deep-rTMS was delivered within the boundaries of the PSI in all participants. CONCLUSION: PSI deep-rTMS provided significant pain relief during 5-day induction sessions compared to sham stimulation.

Abnormal sensory thresholds of dystonic patients are not affected by deep brain stimulation.

BACKGROUND: Unlike motor symptoms, the effects of deep brain stimulation (DBS) on non-motor symptoms associated with dystonia remain unknown. METHODS: The objective of this study was to assess the effects of DBS on evoked experimental pain and cutaneous sensory thresholds in a crossover, double-blind on/off study and compare these results with those of healthy volunteers (HV). RESULTS: Sixteen patients with idiopathic dystonia (39.9 ± 13 years old, n = 14 generalized) with DBS of the globus pallidus internus underwent a battery of quantitative sensory testing and assessment using a pain top-down modulation system (conditioned pain modulation, CPM). Results for the more and less dystonic body regions were compared in on and off stimulation. The patients' results were compared to age- and sex-matched HV. Descending pain modulation CPM responses in dystonic patients (on-DBS, 11.8 ± 40.7; off-DBS, 1.8 ± 22.1) was abnormally low (defective) compared to HV (-15.6 ± 23.5, respectively p = .006 and p = .042). Cold pain threshold and cold hyperalgesia were 54.8% and 95.7% higher in dystonic patients compared to HV. On-DBS CPM correlated with higher Burke-Fahn-Marsden disability score (r = 0.598; p = .014). While sensory and pain thresholds were not affected by DBS on/off condition, pain modulation was abnormal in dystonic patients and tended to be aggravated by DBS. CONCLUSION: The analgesic effects after DBS do not seem to depend on short-duration changes in cutaneous sensory thresholds in dystonic patients and may be related to changes in the central processing of nociceptive inputs.

Sorting pain out of salience: assessment of pain facial expressions in the human fetus.

INTRODUCTION: The question of whether the human fetus experiences pain has received substantial attention in recent times. With the advent of high-definition 4-dimensional ultrasound (4D-US), it is possible to record fetal body and facial expressions. OBJECTIVE: To determine whether human fetuses demonstrate discriminative acute behavioral responses to nociceptive input. METHODS: This cross-sectional study included 5 fetuses with diaphragmatic hernia with indication of intrauterine surgery (fetoscopic endoluminal tracheal occlusion) and 8 healthy fetuses, who were scanned with 4D-US in 1 of 3 conditions: (1) acute pain group: Fetuses undergoing intrauterine surgery were assessed in the preoperative period during the anesthetic injection into the thigh; (2) control group at rest: Facial expressions at rest were recorded during scheduled ultrasound examinations; and (3) control group acoustic startle: Fetal facial expressions were recorded during acoustic stimulus (500-4000 Hz; 60-115 dB). RESULTS: Raters blinded to the fetuses' groups scored 65 pictures of fetal facial expressions based on the presence of 12 items (facial movements). Analyses of redundancy and usefulness excluded 5 items for being of low discrimination capacity (P>0.2). The final version of the pain assessment tool consisted of a total of 7 items: brow lowering/eyes squeezed shut/deepening of the nasolabial furrow/open lips/horizontal mouth stretch/vertical mouth stretch/neck deflection. Odd ratios for a facial expression to be detected in acute pain compared with control conditions ranged from 11 (neck deflection) to 1,400 (horizontal mouth stretch). Using the seven-item final tool, we showed that 5 is the cutoff value discriminating pain from nonpainful startle and rest. CONCLUSIONS: This study inaugurates the possibility to study pain responses during the intrauterine life, which may have implications for the postoperative management of pain after intrauterine surgical interventions.

Prevalence and characteristics of new-onset pain in COVID-19 survivours, a controlled study.

BACKGROUND: We assessed whether COVID-19 is associated with de novo pain and de novo chronic pain (CP). METHODS: This controlled cross-sectional study was based on phone interviews of patients discharged from hospital after COVID-19 compared to the control group composed of individuals hospitalized during the same period due to non-COVID-19 causes. Patients were classified as having previous CP based on the ICD-11/IASP criteria, de novo pain (i.e. any new type of pain, irrespective of the pain status before hospital stay), and de novo CP (i.e. persistent or recurring de novo pain, lasting more than 3 months) after COVID-19. We assessed pain prevalence and its characteristics, including headache profile, pain location, intensity, interference, and its relationship with fatigue, and persistent anosmia. Forty-six COVID-19 and 73 control patients were included. Both groups had similar sociodemographic characteristics and past medical history. RESULTS: Length of in-hospital-stay and ICU admission rates were significantly higher amongst COVID-19 survivours, while mechanical ventilation requirement was similar between groups. Pre-hospitalisation pain was lower in COVID-19 compared to control group (10.9% vs. 42.5%; p = 0.001). However, the COVID-19 group had a significantly higher prevalence of de novo pain (65.2% vs. 11.0%, p = 0.001), as well as more de novo headache (39.1%) compared to controls (2.7%, p = 0.001). New-onset CP was 19.6% in COVID-19 patients and 1.4% (p = 0.002) in controls. These differences remained significant (p = 0.001) even after analysing exclusively (COVID: n = 40; controls: n = 34) patients who did not report previous pain before the hospital stay. No statistically significant differences were found for mean new-onset pain intensity and interference with daily activities between both groups. COVID-19 pain was more frequently located in the head/neck and lower limbs (p < 0.05). New-onset fatigue was more common in COVID-19 survivours necessitating inpatient hospital care (66.8%) compared to controls (2.5%, p = 0.001). COVID-19 patients who reported anosmia had more new-onset pain (83.3%) compared to those who did not (48.0%, p = 0.024). CONCLUSION: COVID-19 was associated with a significantly higher prevalence of de novo CP, chronic daily headache, and new-onset pain in general, which was associated with persistent anosmia. SIGNIFICANCE: There exists de novo pain in a substantial number of COVID-19 survivours, and some develop chronic pain. New-onset pain after the infection was more common in patients who reported anosmia after hospital discharge.

Balloon compression vs radiofrequency for primary trigeminal neuralgia: a randomized, controlled trial.

ABSTRACT: Surgical procedures are necessary in up to 50% of trigeminal neuralgia patients. Although radiofrequency (RF) is more widely used, it is associated with high intraprocedural costs and long technical learning time. Other simpler procedures such as balloon compression (BC) require a lower training period and have significant lower costs. We evaluated the effects of BC and RF in pain control in primary trigeminal neuralgia in a randomized, double-blinded, head-to-head trial. Individuals were randomly allocated in 1 of 2 groups: BC and RF. Throughout pain, psychological and quality of life measurements were performed at baseline and after surgery. The main outcome was the worst pain in the last 24 hours (0-10) at 6 months postoperatively. After the inclusion of half of the estimated sample, a preplanned interim analysis was performed when 33 patients (62.1 ± 9.4 y.) completed the study. Pain intensity (confidence interval [CI] 95% 0.6 to 3.8, and -0.6 to 2.2, for BC and RF) did not significantly differ. Complications, interference of pain in daily life (CI 95% -0.1 to 2.3 and -0.4 to 2.3, for BC and RF), neuropathic pain symptoms (CI 95% 1.7 to 3.6 and 3.0 to 5.7, for BC and RF), mood (CI 95% 4.8 to 11.5 and 5.5 to 15.1, BC and RF, respectively), medication use, and quality of life (CI 95% 80.4 to 93.1 and 83.9 to 94.2, for BC and RF) were also not different. Radiofrequency presented more paresthetic symptoms than BC at 30 days after intervention. Based on these results, the study was halted due to futility because BC was not superior to RF.

Little Brain, Big Expectations.

The cerebellum has been implicated in the mechanisms of several movement disorders. With the recent reports of successful modulation of its functioning, this highly connected structure has emerged as a promising way to provide symptomatic relief not yet obtained by usual treatments. Here we review the most relevant papers published to date, the limitations and gaps in literature, discuss why several papers have failed in showing efficacy, and present a new way of stimulating the cerebellum. References for this critique review were identified by searches on PubMed for the terms "Parkinson's disease", "ataxia", "dystonia", "tremor", and "dyskinesias" in combination with the type of stimulation and the stimulation site. Studies conducted thus far have shed light on the potential of cerebellar neuromodulation for attenuating symptoms in patients with some forms of isolated and combined dystonia, dyskinesia in Parkinson's disease, and neurodegenerative ataxia. However, there is still a high heterogeneity of results and uncertainty about the possibility of maintaining long-term benefits. Because of the complicated architecture of the cerebellum, the modulation techniques employed may have to focus on targeting the activity of the cerebellar nuclei rather than the cerebellar cortex. Measures of cerebellar activity may reduce the variability in outcomes.

Transcutaneous magnetic spinal cord stimulation for freezing of gait in Parkinson's disease.

Dopaminergic drugs partially alleviate gait problems in Parkinson's disease, but the effects are not sustained in the long-term. Particularly, the freezing of gait directly impacts patients' quality of life. Experimental epidural spinal cord stimulation (SCS) studies have suggested positive effects on locomotion among PD patients, but the effects of non-invasive stimulation have never been explored. Here, we investigated in a prospective, open-label, pilot study the efficacy and safety of non-invasive magnetic stimulation of the spinal cord in five patients with PD who experienced gait problems, including freezing of gait. A trial of transcutaneous magnetic SCS was performed at the level of the fifth thoracic vertebra. The primary outcome was the change in freezing of gait 7 days after stimulation. Secondary outcome measures included changes in gait speed and UPDRS part III. After non-invasive spinal cord stimulation, patients experienced a 22% improvement in freezing of gait (p = 0.040) and 17.4% improvement in the UPDRS part III (p = 0.042). Timed up and go times improved by 48.2%, although this did not reach statistical significance (p = 0.06). Patients' global impression of change was 'much improved' for four patients. Improvement in gait after stimulation was reversible, since it returned to baseline scores 4 weeks after stimulation. No severe side effects were recorded. This pilot study suggests that transcutaneous magnetic spinal cord stimulation is feasible and can potentially improve gait problems in PD, without severe adverse effects. Large scale phase II trials are needed to test this hypothesis.

Sifting the wheat from the chaff? Evidence for the existence of an asymmetric fibromyalgia phenotype.

BACKGROUND: The different phenotypic presentations of fibromyalgia (FM) have been infrequently studied and may have diagnostic and therapeutic implications. The aim of this study was to explore differences between FM patients with classical symmetric (s-FM) presentation and FM patients with marked asymmetric (a-FM) pain. METHODS: We performed two consecutive cross-sectional studies on FM patients and matched healthy volunteers (HV). FM patients were divided into a-FM (and s-FM groups according to their score of pain intensity on each body side; patients with a difference of ≥40 mm in VAS between left and right sides were classified as a-FM, otherwise classified as s-FM. Participants (FM = 32; HV = 31) were assessed for clinical, cortical excitability (CE), quantitative sensory testing (QST; study 1), and intraepidermal nerve fibre density (IENFD) determinations (study 2). RESULTS: While pain intensity did not significantly differ between s-FM and a-FM patients, pain interference in daily activities was significantly higher in the a-FM as compared to the s-FM group (54.7 ± 8.9 and 37.6 ± 13.5; p < .0001). PPT was significantly lower in the more painful side of a-FM as compared to the HV (27.7 ± 7.9 and 49.9 ± 13.0; p < .0001), while PPT in the less painful side of a-FM was significantly higher than PPT values in the s-FM (35.8 ± 8.3 and 27.7 ± 5.5; p = .031). S-FM and a-FM had significantly abnormal intracortical inhibition values on CE measurements compared to HV. There were no significant differences in IENFD between groups. CONCLUSIONS: Within the current FM criteria, there exist different phenotypes with clinical, psychophysics, and neurophysiological findings that are not related to peripheral IENFD abnormalities. SIGNIFICANCE: Current fibromyalgia criteria may contain different phenotypes of fibromyalgia based on the lateralization of pain.

Characterization of pain syndromes in patients with neuromyelitis optica.

BACKGROUND: Pain is common and refractory in spinal cord injury (SCI). Currently, most studies evaluated pain in male-predominant traumatic-SCI. Also, concomitant secondary pain syndromes and its temporal evolution were seldom reported. METHODS: We aimed to prospectively describe the main and secondary pain and its associated factors in inflammatory-SCI evaluating neuromyelitis optica (NMO) patients. In-remission NMO patients underwent neurological, imaging and autoantibody evaluations. Questionnaires detailing main and secondary pains, functional state, mood, catastrophizing, quality of life (QoL) and "non-motor symptoms" were used at two time points. RESULTS: Pain was present in 53 (73.6%) of the 72 patients included. At-level neuropathic pain was the most common main pain syndrome, affecting 32 subjects (60.4% of those with pain). Over 70% (n = 38) of this cohort reported two pain syndromes. Those without pain were significantly younger (26.1 ± 12.7 y.o. in those without pain and 40.1 ± 12.5, 37.2 ± 11.4 y.o. in those whose main pain was neuropathic and non-neuropathic, respectively, p = .001), and no differences in the inflammatory status were observed between groups. On follow-up, one-fifth (n = 11) had a different main pain syndrome from the first visit. Pain impacted QoL as much as disability and motor strength. CONCLUSION: Pain is a prevalent and disabling non-motor symptom in NMO-SCI. Most patients experience more than one pain syndrome which can change in time even in the absence of clinical relapse. Age of the inflammatory-SCI was a major determinant of pain. Acknowledging temporal changes and multiplicity of pain syndromes in NMO-SCI may give insights into more precise designs of clinical trials and general management of pain in SCI. SIGNIFICANCE: In this longitudinal study with NMO-related SCI, pain affected almost three-quarters of patients with NMO. Over 70% have more than one pain syndrome and at-level neuropathic pain is the most common type of pain syndrome. Patients without pain were significantly younger but had the same burden of inflammatory lesions than those with pain. During follow-up, up to one fifth of patients presented with changes in the main pain syndromes, which can occur even in the absence of clinical activity of the inflammatory disease. In this cohort, Pain affected quality of life as much as disability or motor strength.

Connectivity Patterns of Subthalamic Stimulation Influence Pain Outcomes in Parkinson's Disease.

Background: Pain is highly prevalent in Parkinson's disease and is associated with significant reduction in health-related quality of life. Subthalamic deep brain stimulation can produce significant pain relief in a subset of patients after surgery. However, the mechanism by which deep brain stimulation modulates sensory function in Parkinson's disease remains uncertain. Objective: To describe the motor and pain outcomes of deep brain stimulation applied to a series of patients with Parkinson's disease and to determine whether the structural connectivity between the volume of tissue activated and different regions of the brain was associated with the changes of these outcomes after surgery. Methods: Data from a long-term prospective cohort of 32 Parkinson's disease patients with subthalamic stimulation were combined with available human connectome to identify connections consistently associated with clinical improvement (Unified Parkinson Disease Rating Scale), pain intensity, and experimental cold pain threshold after surgery. Results: The connectivity between the volume of tissue activated and a distributed network of sensory brain regions (prefrontal, insular and cingulate cortex, and postcentral gyrus) was inversely correlated with pain intensity improvement and reduced sensitivity to cold pain after surgery (p < 0.01). The connectivity strength with the supplementary motor area positively correlated with motor and pain threshold improvement (p < 0.05). Conclusions: These data suggest that the pattern of the connectivity between the region stimulated and specific brain cortical area might be responsible, in part, for the successful control of motor and pain symptoms by subthalamic deep brain stimulation in Parkinson's disease.

Altered cortical excitability in persistent idiopathic facial pain.

INTRODUCTION: Persistent idiopathic facial pain is a refractory and disabling condition of unknown mechanism and etiology. It has been suggested that persistent idiopathic facial pain patients have not only peripheral generators of pain, but also central nervous system changes that would contribute to the persistence of symptoms. We hypothesized that persistent idiopathic facial pain would have changes in brain cortical excitability as measured by transcranial magnetic stimulation compared to healthy controls. METHODS: Twenty-nine persistent idiopathic facial pain patients were compared to age- and sex-matched healthy controls and underwent cortical excitability measurements by transcranial magnetic stimulation applied to the cortical representation of the masseter muscle of both hemispheres. Single-pulse stimulation was used to measure the resting motor threshold and suprathreshold motor-evoked potentials. Paired-pulse stimulation was used to assess short intracortical inhibition and intracortical facilitation. Clinical pain and associated symptoms were assessed with validated tools. RESULTS: Spontaneous pain was found in 27 (93.1%) and provoked pain was found in two (6.9%) persistent idiopathic facial pain patients. The motor-evoked potentials at 120% and 140% were significantly lower for both hemispheres compared to controls. Persistent idiopathic facial pain patients had lower short-interval intracortical inhibition compared with controls. These changes were correlated with some aspects of quality of life, and higher mood symptoms. These neurophysiological alterations were not influenced by analgesic medication, as similar changes were observed in patients with or without central-acting drugs. CONCLUSIONS: Persistent idiopathic facial pain is associated with changes in intracortical modulation involving GABAergic mechanisms, which may be related to certain aspects of the pathophysiology of this chronic pain condition. Trial registration: NTC01746355.