Left-sided epileptiform activity influences language lateralization in right mesial temporal sclerosis.

OBJECTIVE: To investigate the association between left epileptiform activity and language laterality indices (LI) in patients with right mesial temporal sclerosis (MTS). METHODS: Twenty-two patients with right MTS and 22 healthy subjects underwent fMRI scanning while performing a language task. LI was calculated in multiple regions of interest (ROI). Data on the presence of left epileptiform abnormalities were obtained during prolonged video-EEG monitoring. RESULTS: After correction for multiple comparisons, LI was reduced in the middle temporal gyrus in the left interictal epileptiform discharges (IED+) group, compared with the left IED- group (p < 0.05). SIGNIFICANCE: Using a responsive reading naming fMRI paradigm, right MTS patients who presented left temporal interictal epileptiform abnormalities on video-EEG showed decreased LI in the middle temporal gyrus, indicating decreased left middle temporal gyrus activation, increased right middle temporal gyrus activation or a combination of both, demonstrative of language network reorganization, specially in the MTG, in this patient population. PLAIN LANGUAGE SUMMARY: This research studied 22 patients with right mesial temporal sclerosis (a specific type of epilepsy) comparing them to 22 healthy individuals. Participants were asked to perform a language task while undergoing a special brain imaging technique (fMRI). The findings showed that patients with epilepsy displayed a change in the area of the brain typically responsible for language processing. This suggests that their brains may have adapted due to their condition, altering the way language is processed.

Subacute Partially Reversible Leukoencephalopathy Expands the Aicardi-Goutières Syndrome Phenotype.

OBJECTIVE: To report a series of atypical presentations of Aicardi-Goutières syndrome. METHODS: Clinical, neuroimaging, and genetic data. RESULTS: We report a series of six unrelated patients (five males) with a subacute loss of developmental milestones, pyramidal signs, and regression of communication abilities, with onset at ages ranging from 7 to 20 months, reaching a nadir after 4 to 24 weeks. A remarkable improvement of lost abilities occurred in the follow-up, and they remained with residual spasticity and dysarthria but preserved cognitive function. Immunization or febrile illness occurred before disease onset in all patients. CSF was normal in two patients, and in four, borderline or mild lymphocytosis was present. A brain CT scan disclosed a subtle basal ganglia calcification in one of six patients. Brain MRI showed asymmetric signal abnormalities of white matter with centrum semi-ovale involvement in five patients and a diffuse white matter abnormality with contrast enhancement in one. Four patients were diagnosed and treated for acute demyelinating encephalomyelitis (ADEM). Brain imaging was markedly improved with one year or more of follow-up (average of 7 years), but patients remained with residual spasticity and dysarthria without cognitive impairment. Demyelination relapse occurred in a single patient four years after the first event. Whole-exome sequencing (WES) was performed in all patients: four of them disclosed biallelic pathogenic variants in RNASEH2B (three homozygous p.Ala177Thr and one compound heterozygous p.Ala177Thr/p.Gln58*) and in two of them the same homozygous deleterious variants in RNASEH2A (p.Ala249Val). CONCLUSIONS: This report expands the phenotype of AGS to include subacute developmental regression with partial clinical and neuroimaging improvement. Those clinical features might be misdiagnosed as ADEM.

Development and Validation of the Dystonia-Pain Classification System: A Multicenter Study.

BACKGROUND: Dystonia is associated with disabling nonmotor symptoms like chronic pain (CP), which is prevalent in dystonia and significantly impacts the quality of life (QoL). There is no validated tool for assessing CP in dystonia, which substantially hampers pain management. OBJECTIVE: The aim was to develop a CP classification and scoring system for dystonia. METHODS: A multidisciplinary group was established to develop the Dystonia-Pain Classification System (Dystonia-PCS). The classification of CP as related or unrelated to dystonia was followed by the assessment of pain severity score, encompassing pain intensity, frequency, and impact on daily living. Then, consecutive patients with inherited/idiopathic dystonia of different spatial distribution were recruited in a cross-sectional multicenter validation study. Dystonia-PCS was compared to validated pain, mood, QoL, and dystonia scales (Brief Pain Inventory, Douleur Neuropathique-4 questionnaire, European QoL-5 Dimensions-3 Level Version, and Burke-Fahn-Marsden Dystonia Rating Scale). RESULTS: CP was present in 81 of 123 recruited patients, being directly related to dystonia in 82.7%, aggravated by dystonia in 8.8%, and nonrelated to dystonia in 7.5%. Dystonia-PCS had excellent intra-rater (Intraclass Correlation Coefficient - ICC: 0.941) and inter-rater (ICC: 0.867) reliability. In addition, pain severity score correlated with European QoL-5 Dimensions-3 Level Version's pain subscore (r = 0.635, P < 0.001) and the Brief Pain Inventory's severity and interference scores (r = 0.553, P < 0.001 and r = 0.609, P < 0.001, respectively). CONCLUSIONS: Dystonia-PCS is a reliable tool to categorize and quantify CP impact in dystonia and will help improve clinical trial design and management of CP in patients affected by this disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Exploring clinical outcomes in patients with idiopathic/inherited isolated generalized dystonia and stimulation of the subthalamic region.

BACKGROUND: Deep Brain Stimulation (DBS) is an established treatment option for refractory dystonia, but the improvement among the patients is variable. OBJECTIVE: To describe the outcomes of DBS of the subthalamic region (STN) in dystonic patients and to determine whether the volume of tissue activated (VTA) inside the STN or the structural connectivity between the area stimulated and different regions of the brain are associated with dystonia improvement. METHODS: The response to DBS was measured by the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) before and 7 months after surgery in patients with generalized isolated dystonia of inherited/idiopathic etiology. The sum of the two overlapping STN volumes from both hemispheres was correlated with the change in BFM scores to assess whether the area stimulated inside the STN affects the clinical outcome. Structural connectivity estimates between the VTA (of each patient) and different brain regions were computed using a normative connectome taken from healthy subjects. RESULTS: Five patients were included. The baseline BFM motor and disability subscores were 78.30 ± 13.55 (62.00-98.00) and 20.60 ± 7.80 (13.00-32.00), respectively. Patients improved dystonic symptoms, though differently. No relationships were found between the VTA inside the STN and the BFM improvement after surgery (p = 0.463). However, the connectivity between the VTA and the cerebellum structurally correlated with dystonia improvement (p = 0.003). CONCLUSIONS: These data suggest that the volume of the stimulated STN does not explain the variance in outcomes in dystonia. Still, the connectivity pattern between the region stimulated and the cerebellum is linked to outcomes of patients.

ANTECEDENTES: A estimulação cerebral profunda (ECP) é um tratamento estabelecido para distonias refratárias. Porém, a melhora dos pacientes é variável. OBJETIVO: O objetivo do estudo foi descrever os desfechos da ECP da região do núcleo subtalâmico (NST) e determinar se o volume de tecido ativado (VTA) dentro do NST ou se a conectividade estrutural entre a área estimulada e diferentes regiões cerebrais estão associadas a melhora da distonia. MéTODOS: A resposta da ECP em pacientes com distonia generalizada isolada de etiologia hereditária/idiopática foi mensurada pela escala de Burke-Fahr-Marsden Dystonia Rating Scale (BFM) antes e 7 meses após a cirurgia. A soma dos volumes do NST nos dois hemisférios foi correlacionada com a melhora nos escores do BFM para avaliar se a área estimulada dentro do NST afeta o desfecho clínico. A conectividade estrutural estimada entre o VTA de cada paciente e as diferentes regiões cerebrais foram computadas usando um conectoma normativo retirado de indivíduos saudáveis. RESULTADOS: Cinco pacientes com idade de 40,00 ± 7,30 anos foram incluídos. O BFM motor e de incapacidade basal eram de 78,30 ± 13,55 (62,00­98,00) e 20,60 ± 7,80 (13,00­32,00), respectivamente. Os pacientes melhoraram com a cirurgia, mas com variabilidade. Não houve relação entre o VTA dentro do NST e a melhora do BFM após a cirurgia (p = 0.463). Entretanto, a conectividade estrutural entre o VTA e o cerebelo correlacionaram com a melhora da distonia (p = 0.003). CONCLUSãO: Os dados sugerem que o VTA dentro do NST não explica a variabilidade do desfecho clínico na distonia. Porém, o padrão de conectividade entre a região estimulada e o cerebelo foi relacionada com o desfecho dos pacientes.

Exploring clinical outcomes in patients with idiopathic/inherited isolated generalized dystonia and stimulation of the subthalamic region / Explorando os desfechos clínicos em pacientes com distonia idiopática/hereditária generalizada isolada submetidos a estimulação da região subtalâmica

Abstract Background Deep Brain Stimulation (DBS) is an established treatment option for refractory dystonia, but the improvement among the patients is variable. Objective To describe the outcomes of DBS of the subthalamic region (STN) in dystonic patients and to determine whether the volume of tissue activated (VTA) inside the STN or the structural connectivity between the area stimulated and different regions of the brain are associated with dystonia improvement. Methods The response to DBS was measured by the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) before and 7 months after surgery in patients with generalized isolated dystonia of inherited/idiopathic etiology. The sum of the two overlapping STN volumes from both hemispheres was correlated with the change in BFM scores to assess whether the area stimulated inside the STN affects the clinical outcome. Structural connectivity estimates between the VTA (of each patient) and different brain regions were computed using a normative connectome taken from healthy subjects. Results Five patients were included. The baseline BFM motor and disability subscores were 78.30 ± 13.55 (62.00-98.00) and 20.60 ± 7.80 (13.00-32.00), respectively. Patients improved dystonic symptoms, though differently. No relationships were found between the VTA inside the STN and the BFM improvement after surgery (p = 0.463). However, the connectivity between the VTA and the cerebellum structurally correlated with dystonia improvement (p = 0.003). Conclusions These data suggest that the volume of the stimulated STN does not explain the variance in outcomes in dystonia. Still, the connectivity pattern between the region stimulated and the cerebellum is linked to outcomes of patients.

Resumo Antecedentes A estimulação cerebral profunda (ECP) é um tratamento estabelecido para distonias refratárias. Porém, a melhora dos pacientes é variável. Objetivo O objetivo do estudo foi descrever os desfechos da ECP da região do núcleo subtalâmico (NST) e determinar se o volume de tecido ativado (VTA) dentro do NST ou se a conectividade estrutural entre a área estimulada e diferentes regiões cerebrais estão associadas a melhora da distonia. Métodos A resposta da ECP em pacientes com distonia generalizada isolada de etiologia hereditária/idiopática foi mensurada pela escala de Burke-Fahr-Marsden Dystonia Rating Scale (BFM) antes e 7 meses após a cirurgia. A soma dos volumes do NST nos dois hemisférios foi correlacionada com a melhora nos escores do BFM para avaliar se a área estimulada dentro do NST afeta o desfecho clínico. A conectividade estrutural estimada entre o VTA de cada paciente e as diferentes regiões cerebrais foram computadas usando um conectoma normativo retirado de indivíduos saudáveis. Resultados Cinco pacientes com idade de 40,00 ± 7,30 anos foram incluídos. O BFM motor e de incapacidade basal eram de 78,30 ± 13,55 (62,00-98,00) e 20,60 ± 7,80 (13,00-32,00), respectivamente. Os pacientes melhoraram com a cirurgia, mas com variabilidade. Não houve relação entre o VTA dentro do NST e a melhora do BFM após a cirurgia (p = 0.463). Entretanto, a conectividade estrutural entre o VTA e o cerebelo correlacionaram com a melhora da distonia (p = 0.003). Conclusão Os dados sugerem que o VTA dentro do NST não explica a variabilidade do desfecho clínico na distonia. Porém, o padrão de conectividade entre a região estimulada e o cerebelo foi relacionada com o desfecho dos pacientes.

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.

Should the Globus Pallidus Targeting Be Refined in Dystonia?

BACKGROUND AND STUDY AIMS: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a highly effective therapy for primary generalized and focal dystonias, but therapeutic success is compromised by a nonresponder rate of up to 20%. Variability in electrode placement and in tissue stimulated inside the GPi may explain in part different outcomes among patients. Refinement of the target within the pallidal area could be helpful for surgery planning and clinical outcomes. The objective of this study was to discuss current and potential methodological (somatotopy, neuroimaging, and neurophysiology) aspects that might assist neurosurgical targeting of the GPi, aiming to treat generalized or focal dystonia. METHODS: We selected published studies by searching electronic databases and scanning the reference lists for articles that examined the anatomical and electrophysiologic aspects of the GPi in patients with idiopathic/inherited dystonia who underwent functional neurosurgical procedures. RESULTS: The sensorimotor sector of the GPi was the best target to treat dystonic symptoms, and was localized at its lateral posteroventral portion. The effective volume of tissue activated (VTA) to treat dystonia had a mean volume of 153 mm3 in the posterior GPi area. Initial tractography studies evaluated the close relation between the electrode localization and pallidothalamic tract to control dystonic symptoms.Regarding the somatotopy, the more ventral, lateral, and posterior areas of the GPi are associated with orofacial and cervical representation. In contrast, the more dorsal, medial, and anterior areas are associated with the lower limbs; between those areas, there is the representation of the upper limb. Excessive pallidal synchronization has a peak at the theta band of 3 to 8 Hz, which might be responsible for generating dystonic symptoms. CONCLUSIONS: Somatotopy assessment of posteroventral GPi contributes to target-specific GPi sectors related to segmental body symptoms. Tractography delineates GPi output pathways that might guide electrode implants, and electrophysiology might assist in pointing out areas of excessive theta synchronization. Finally, the identification of oscillatory electrophysiologic features that correlate with symptoms might enable closed-loop approaches in the future.

Improvement of Non-motor Symptoms and Quality of Life After Deep Brain Stimulation for Refractory Dystonia: A 1-Year Follow-Up.

Introduction: Deep brain stimulation (DBS) is a treatment option for refractory dystonia's motor symptoms, while its non-motor symptoms (NMS) have been less systematically assessed. We aimed to describe the effects of DBS on NMS in refractory generalized inherited/idiopathic dystonia prospectively. Methods: We evaluated patients before and 1 year after DBS surgery and applied the following scales: Burke-Fahn-Marsden Rating Scale (BFMRS), NMS Scale for Parkinson's Disease (NMSS-PD), Parkinson's Disease Questionnaire-8, short-form Brief Pain Inventory (BPI), Neuropathic Pain Symptom Inventory (NPSI), and short-form McGill Pain Questionnaire (MPQ). Results: Eleven patients (38.35 ± 11.30 years) underwent surgery, all with generalized dystonia. Motor BFMRS subscore was 64.36 ± 22.94 at baseline and 33.55 ± 17.44 1 year after DBS surgery (47.9% improvement, p = 0.003). NMSS-PD had a significant change 12 months after DBS, from 70.91 ± 59.07 to 37.18 ± 55.05 (47.5% improvement, p = 0.013). NMS changes were mainly driven by changes in the gastrointestinal (p = 0.041) and miscellaneous domains (p = 0.012). Seven patients reported chronic pain before DBS and four after it. BPI's severity and interference scores were 4.61 ± 2.84 and 4.12 ± 2.67, respectively, before surgery, and 2.79 ± 2.31 (0.00-6.25) and 1.12 ± 1.32 (0.00-3.00) after, reflecting a significant improvement (p = 0.043 and p = 0.028, respectively). NPSI score was 15.29 ± 13.94 before, while it was reduced to 2.29 ± 2.98 afterward (p = 0.028). MPQ's total score was 9.00 ± 3.32 before DBS, achieving 2.71 ± 2.93 after (p = 0.028). Conclusions: DBS improves NMS in generalized inherited/idiopathic dystonia, including chronic pain.

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.

Rescue Subthalamic Deep Brain Stimulation for Refractory Meige Syndrome.

Meige syndrome is a segmental form of dystonia. It is a disabling disease, especially when refractory to treatment with botulinum toxin. A well-established therapeutic option is deep brain stimulation (DBS), and the target in bilateral globus pallidus internus (GPi DBS) demonstrated satisfactory short- and long-term efficacy. However, some patients present minor or suboptimal responses after GPi DBS, and in those cases, rescue DBS may be appropriate. The present case illustrates a good outcome after subthalamic nucleus (STN) and not after GPi DBS (considering that both were well positioned and had adequate programming). The larger dimension of the GPi and its somatotopic organization, with the stimulation outside the "face region," could explain our outcomes.

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.

The Parkinson disease pain classification system: results from an international mechanism-based classification approach.

ABSTRACT: Pain is a common nonmotor symptom in patients with Parkinson disease (PD) but the correct diagnosis of the respective cause remains difficult because suitable tools are lacking, so far. We developed a framework to differentiate PD- from non-PD-related pain and classify PD-related pain into 3 groups based on validated mechanistic pain descriptors (nociceptive, neuropathic, or nociplastic), which encompass all the previously described PD pain types. Severity of PD-related pain syndromes was scored by ratings of intensity, frequency, and interference with daily living activities. The PD-Pain Classification System (PD-PCS) was compared with classic pain measures (ie, brief pain inventory and McGill pain questionnaire [MPQ], PDQ-8 quality of life score, MDS-UPDRS scores, and nonmotor symptoms). 159 nondemented PD patients (disease duration 10.2 ± 7.6 years) and 37 healthy controls were recruited in 4 centers. PD-related pain was present in 122 patients (77%), with 24 (15%) suffering one or more syndromes at the same time. PD-related nociceptive, neuropathic, or nociplastic pain was diagnosed in 87 (55%), 25 (16%), or 35 (22%), respectively. Pain unrelated to PD was present in 35 (22%) patients. Overall, PD-PCS severity score significantly correlated with pain's Brief Pain Inventory and MPQ ratings, presence of dyskinesia and motor fluctuations, PDQ-8 scores, depression, and anxiety measures. Moderate intrarater and interrater reliability was observed. The PD-PCS is a valid and reliable tool for differentiating PD-related pain from PD-unrelated pain. It detects and scores mechanistic pain subtypes in a pragmatic and treatment-oriented approach, unifying previous classifications of PD-pain.

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

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.

Pharmacological treatment of central neuropathic pain: consensus of the Brazilian Academy of Neurology / Tratamento farmacológico da dor neuropática central: consenso da Academia Brasileira de Neurologia

ABSTRACT 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.

RESUMO Introdução: A dor neuropática central (DNC) é frequentemente refratária às estratégias terapêuticas disponíveis e há poucas opções de tratamento baseado em evidência. Muitos pacientes com dor neuropática não são diagnosticados ou tratados adequadamente. Desse modo, recomendações baseadas em consenso, adaptadas à disponibilidade de medicamentos no país, são necessárias para guiar decisões clínicas. Objetivo: Desenvolver recomendações para o tratamento da DNC no Brasil. Métodos: Revisão sistemática, metanálise e discussão dos resultados entre especialistas e pesquisadores da área, considerando eficácia, perfil de eventos adversos, custo e disponibilidade do fármaco na saúde pública. Resultados: Foram encontrados 44 estudos sobre tratamento da DNC, dos quais 20 foram incluídos na análise qualitativa e 15, na quantitativa. Classificaram-se as medicações em primeira, segunda e terceira linhas de tratamento, baseando-se em revisão sistemática, meta-análise e opinião de especialistas. Como primeira linha, foram incluídos gabapentina, duloxetina e antidepressivos tricíclicos. Como segunda, venlafaxina, pregabalina para DNC secundária à lesão medular, lamotrigina para DNC pós-acidente vascular cerebral e, em associação aos fármacos de primeira linha, opioides fracos, em particular tramadol. Para os pacientes refratários, opioides fortes (metadona e oxicodona) e canabidiol/delta-9-tetrahidrocanabinol foram classificados como terceira linha de tratamento, em associação com drogas de primeira ou segunda linha, e, para DNC na esclerose múltipla, dronabinol. Conclusões: Os estudos que abordam o tratamento da DNC são escassos e heterogêneos, e parte significativa das recomendações é baseada em opiniões de especialistas. A abordagem da DNC deve ser individualizada, levando em conta a disponibilidade de medicação, o perfil de efeitos adversos, incluindo risco de dependência e as comorbidades do paciente.

Deep brain stimulation treatment in dystonia: a bibliometric analysis.

BACKGROUND: Dystonia is a heterogeneous disorder that, when refractory to medical treatment, may have a favorable response to deep brain stimulation (DBS). A practical way to have an overview of a research domain is through a bibliometric analysis, as it makes it more accessible for researchers and others outside the field to have an idea of its directions and needs. OBJECTIVE: To analyze the 100 most cited articles in the use of DBS for dystonia treatment in the last 30 years. METHODS: The research protocol was performed in June 2019 in Elsevier's Scopus database, by retrieving the most cited articles regarding DBS in dystonia. We analyzed authors, year of publication, country, affiliation, and targets of DBS. RESULTS: Articles are mainly published in Movement Disorders (19%), Journal of Neurosurgery (9%), and Neurology (9%). European countries offer significant contributions (57% of our sample). France (192.5 citations/paper) and Germany (144.1 citations/paper) have the highest citation rates of all countries. The United States contributes with 31% of the articles, with 129.8 citations/paper. The publications are focused on General outcomes (46%), followed by Long-term outcomes (12.5%), and Complications (11%), and the leading type of dystonia researched is idiopathic or inherited, isolated, segmental or generalized dystonia, with 27% of articles and 204.3 citations/paper. CONCLUSIONS: DBS in dystonia research is mainly published in a handful of scientific journals and focused on the outcomes of the surgery in idiopathic or inherited, isolated, segmental or generalized dystonia, and with globus pallidus internus as the main DBS target.

Deep brain stimulation treatment in dystonia: a bibliometric analysis / Estimulação cerebral profunda no tratamento de distonia: uma análise bibliométrica

ABSTRACT Background: Dystonia is a heterogeneous disorder that, when refractory to medical treatment, may have a favorable response to deep brain stimulation (DBS). A practical way to have an overview of a research domain is through a bibliometric analysis, as it makes it more accessible for researchers and others outside the field to have an idea of its directions and needs. Objective: To analyze the 100 most cited articles in the use of DBS for dystonia treatment in the last 30 years. Methods: The research protocol was performed in June 2019 in Elsevier's Scopus database, by retrieving the most cited articles regarding DBS in dystonia. We analyzed authors, year of publication, country, affiliation, and targets of DBS. Results: Articles are mainly published in Movement Disorders (19%), Journal of Neurosurgery (9%), and Neurology (9%). European countries offer significant contributions (57% of our sample). France (192.5 citations/paper) and Germany (144.1 citations/paper) have the highest citation rates of all countries. The United States contributes with 31% of the articles, with 129.8 citations/paper. The publications are focused on General outcomes (46%), followed by Long-term outcomes (12.5%), and Complications (11%), and the leading type of dystonia researched is idiopathic or inherited, isolated, segmental or generalized dystonia, with 27% of articles and 204.3 citations/paper. Conclusions: DBS in dystonia research is mainly published in a handful of scientific journals and focused on the outcomes of the surgery in idiopathic or inherited, isolated, segmental or generalized dystonia, and with globus pallidus internus as the main DBS target.

RESUMO Introdução: A distonia é uma doença heterogênea que, quando refratária ao tratamento medicamentoso, pode ter uma resposta favorável à estimulação encefálica profunda (EEP). Uma forma prática de ter uma visão desta área de pesquisa é por meio de análise bibliométrica, pois permite aos pesquisadores e terceiros a terem uma ideia das tendências e necessidades da área. Objetivo: Analisar os 100 artigos mais citados no tratamento de distonia pelo uso de EEP nos últimos 30 anos. Métodos: O protocolo de pesquisa foi realizado em junho de 2019 através da base de dados Scopus da Elsevier, em que se obteve os artigos mais citados na área de tratamento de distonia com EEP. Analisaram-se variáveis como autores, ano de publicação, país, afiliação, e alvos de EEP. Resultados: Os artigos foram principalmente publicados principalmente na Movement Disorders (19%), no Journal of Neurosurgery (9%), e na Neurology (9%). Os países europeus oferecem contribuições significativas (57% da amostra). A França (192,5 citações/artigo) e a Alemanha (144,1 citações/artigo) possuem as mais altas taxas de citações dentre todos os países. Os Estados Unidos contribuem com 31% dos artigos da amostra (129,8 citações/artigo). As publicações focaram em Desfechos gerais (46%), seguido de Desfechos a longo prazo (12,5%), e Complicações (11%). O principal tipo de distonia pesquisado foi distonia generalizada ou segmentar, idiopática ou hereditária, isolada, abrangendo 27% dos artigos e 204,3 citações/artigo. Conclusões: A pesquisa de EEP em distonia é publicada em seletos periódicos científicos e foca nos desfechos da cirurgia, nas distonias generalizadas ou segmentares, idiopáticas ou hereditárias, isoladas, sendo o globus pallidus internus o principal alvo da EEP.

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.