Burst Transspinal Magnetic Stimulation Alleviates Nociceptive Pain in Parkinson Disease-A Pilot Phase II Double-Blind, Randomized Study.

BACKGROUND AND AIMS: Nociception is the most prevalent pain mechanism in Parkinson disease (PD). It negatively affects quality of life, and there is currently no evidence-based treatment for its control. Burst spinal cord stimulation has been used to control neuropathic pain and recently has been shown to relieve pain of nociceptive origin. In this study, we hypothesize that burst transspinal magnetic stimulation (bTsMS) reduces nociceptive pain in PD. MATERIALS AND METHODS: Twenty-six patients were included in a double-blind, sham-controlled, randomized parallel trial design, and the analgesic effect of lower-cervical bTsMS was assessed in patients with nociceptive pain in PD. Five daily induction sessions were followed by maintenance sessions delivered twice a week for seven weeks. The primary outcome was the number of responders (≥ 50% reduction of average pain intensity assessed on a numerical rating scale ranging from 0-10) during the eight weeks of treatment. Mood, quality of life, global impression of change, and adverse events were assessed throughout the study. RESULTS: Twenty-six patients (46.2% women) were included in the study. The number of responders during treatment was significantly higher after active than after sham bTsMS (p = 0.044), mainly owing to the effect of the first week of treatment, when eight patients (61.5%) responded to active and two (15.4%) responded to sham bTsMS (p = 0.006); the number needed to treat was 2.2 at week 1. Depression symptom scores were lower after active (4.0 ± 3.1) than after sham bTsMS (8.7 ± 5.3) (p = 0.011). Patients' global impressions of change were improved after active bTsMS (70.0%) compared with sham bTsMS (18.2%; p = 0.030). Minor adverse events were reported in both arms throughout treatment sessions. One major side effect unrelated to treatment occurred in the active arm (death due to pulmonary embolism). Blinding was effective. CONCLUSION: BTsMS provided significant pain relief and improved the global impression of change in PD in this phase-II trial. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT04546529.

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.

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.

Non-invasive insular stimulation for peripheral neuropathic pain: Influence of target or symptom?

OBJECTIVES: The posterior-superior insula (PSI) has been shown to be a safe and potentially effective target for neuromodulation in peripheral neuropathic pain (PNP) in humans and animal models. However, it remains unknown whether there is a measurable responder profile to PSI stimulation. Two factors were hypothesized to influence the response of repetitive transcranial magnetic stimulation (rTMS) of the PSI: differences in rTMS target (discrete subregions of the PSI) or PNP phenotype. METHODS: This is a secondary analysis from a randomized, double-blind, sham-controlled, cross-over trial assessing PSI-rTMS in PNP (N = 31, 5 days rTMS) (10.1016/j.neucli.2021.06.003). Active PSI-rTMS true responders (>50% pain reduction from baseline after active but not after sham series of treatment) were compared with not true responders, to determine whether they differed with respect to 1) rTMS neuro-navigational target coordinates, and/or 2) specific neuropathic pain symptom inventory (NPSI) clusters (pinpointed pain, evoked pain, and deep pain) at baseline. RESULTS: Mean rTMS target coordinates did not differ between true (n = 45.1%) and not true responders (p = 0.436 for X, p = 0.120 for Y, and p = 0.116 for Z). The Euclidian distance between true and not true responders was 4.04 mm. When comparing differences in responders between NPSI clusters, no participant within the evoked pain cluster was a true responder (p = 0.024). CONCLUSION: Response to PSI-rTMS may depend on pain cluster subtype rather than on differences in targeting within the PSI.

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.

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.

Perioperative care in brain arteriovenous malformations / Cuidados perioperatórios em malformações arteriovenosas encefálicas

The authors provide a review of brain arteriovenous malformations, initially reviewing epidemiological and etiological aspects in addition to the pathophysiology and risk factors associated with bleeding. The emphasis of this review is directed to the clinical and care should be taken since the diagnosis of this pathology, intraoperative management on the viewpoint of the anesthesiologist to the potential complications that occur after resection of the lesion.

Os autores realizam uma revisão sobre malformações arteriovenosas encefálicas, revisando inicialmente aspectos etiológicos e epidemiológicos, além da fisiopatologia e de fatores relacionados com risco de sangramento. A maior ênfase dessa revisão é direcionada para o quadro clínico e para os cuidados que devem ser tomados desde o diagnóstico dessa patologia, o manejo intraoperatório sob o ponto de vista do anestesista, até as possíveis complicações que ocorrem após a ressecção da lesão.