Introduction: To date, clinical trials of deep brain stimulation (DBS) for refractory chronic pain have yielded unsatisfying results. Recent evidence suggests that the posterior insula may represent a promising DBS target for this indication. Methods: We present a narrative review highlighting the theoretical basis of posterior insula DBS in patients with chronic pain. Results: Neuroanatomical studies identified the posterior insula as an important cortical relay center for pain and interoception. Intracranial neuronal recordings showed that the earliest response to painful laser stimulation occurs in the posterior insula. The posterior insula is one of the only regions in the brain whose low-frequency electrical stimulation can elicit painful sensations. Most chronic pain syndromes, such as fibromyalgia, had abnormal functional connectivity of the posterior insula on functional imaging. Finally, preliminary results indicated that high-frequency electrical stimulation of the posterior insula can acutely increase pain thresholds. Conclusion: In light of the converging evidence from neuroanatomical, brain lesion, neuroimaging, and intracranial recording and stimulation as well as non-invasive stimulation studies, it appears that the insula is a critical hub for central integration and processing of painful stimuli, whose high-frequency electrical stimulation has the potential to relieve patients from the sensory and affective burden of chronic pain.

Vagal neurostimulation (VNS) is used for the treatment of epilepsy and major medical-refractory depression. VNS has neuropsychiatric functions and systemic anti-inflammatory activity. The objective of this study is to measure the clinical efficacy and impact of VNS modulation in depressive patients. Six patients with refractory depression were enrolled. Depression symptoms were assessed with the Montgomery–Asberg Depression Rating, and anxiety symptoms with the Hamilton Anxiety Rating Scale. Plasmas were harvested prospectively before the implantation of VNS (baseline) and up to 4 years or more after continuous therapy. Forty soluble molecules were measured in the plasma by multiplex assays. Following VNS, the reduction in the mean depression severity score was 59.9% and the response rate was 87%. Anxiety levels were also greatly reduced. IL-7, CXCL8, CCL2, CCL13, CCL17, CCL22, Flt-1 and VEGFc levels were significantly lowered, whereas bFGF levels were increased (p values ranging from 0.004 to 0.02). This exploratory study is the first to focus on the long-term efficacy of VNS and its consequences on inflammatory biomarkers. VNS may modulate inflammation via an increase in blood–brain barrier integrity and a reduction in inflammatory cell recruitment. This opens the door to new pathways involved in the treatment of refractory depression.

OBJECTIVE: Gamma Knife radiosurgery is recognized as an efficient intervention for the treatment of refractory trigeminal neuralgia (TN). The CyberKnife, a more recent frameless and nonisocentric radiosurgery alternative, has not been studied as extensively for this condition. This study aims to evaluate the clinical outcomes of a first CyberKnife radiosurgery (CKRS) treatment in patients with medically refractory TN. METHODS: A retrospective cohort study of 166 patients (168 procedures) with refractory TN treated from 2009 to 2021 at the Centre Hospitalier de l’Université de Montréal was conducted. The treatment was performed using a CyberKnife (model G4, VSI, or M6). The treatment median maximum dose was 80 (range 70.0–88.9) Gy. RESULTS: Adequate pain relief, evaluated using Barrow Neurological Institute pain scale scores (I–IIIb), was achieved in 146 cases (86.9%). The median latency period before adequate pain relief was 35 (range 0–202) days. The median duration of pain relief for cases with a recurrence of pain was 8.3 (range 0.6–85.0) months. The actuarial rates of maintaining adequate pain relief at 12, 36, and 60 months from the treatment date were 77.0%, 62.5%, and 50.2%, respectively. There was new onset or aggravation of facial numbness in 44 cases (26.2%). This facial numbness was predictive of better maintenance of pain relief (p < 0.001). The maintenance of adequate pain relief was sustained longer in idiopathic cases compared with cases associated with multiple sclerosis (MS; p < 0.001). CONCLUSIONS: In the authors’ experience, CKRS for refractory TN is efficient and safe. The onset or aggravation of facial hypoesthesia after treatment was predictive of a more sustained pain relief, and idiopathic cases had more sustained pain relief in comparison with MS-related cases.

Non‐motor symptoms can severely affect the quality of life of Parkinson's disease‐afflicted patients, with the most common ones being pain, sleep impairments, and neuropsychiatric manifestations. In advanced cases, complex fluctuations of motor and non‐motor symptoms can occur despite optimal medication. Research on deep brain stimulation of the subthalamic nucleus suggests that it may provide benefits for treating non‐motor symptoms in addition to improving motor symptoms. With recent advancements in deep brain stimulation technology, simultaneous recording of local field potentials and delivery of therapeutic stimulation is possible. This opens new possibilities for better understanding the pathophysiology of non‐motor symptoms in Parkinson's disease and for identifying potential electrophysiological biomarkers that accurately represent these symptoms. Specifically, this review aims to highlight potential local field potential biomarkers of non‐motor symptoms in the subthalamic nucleus. The main findings indicate that activities in the beta frequency band are associated with nociception and sleep impairments such as insomnia and rapid eye movement sleep behavior disorders. Additionally, activities in the theta and alpha frequency bands seem to reflect neurocognitive manifestations, including depression and impulse control disorders. A better understanding of these biomarkers could improve the clinical management of non‐motor symptoms in Parkinson's disease. They hold promise for adjusting deep brain stimulation parameters in open‐loop settings and might eventually be applied in closed‐loop deep brain stimulation systems, though their true impact remains uncertain.

Background: The outcomes of radiosurgery for trigeminal neuralgia (TN) in patients with multiple sclerosis (MS) are not as extensively assessed as those for idiopathic or classical TN cases. Objective: Evaluate the safety and efficacy of radiosurgery for TN in MS patients and identify potential predictors of successful outcomes. Methods: A retrospective single-institution cohort study with patients treated between 2009 and 2022 was performed. Fifty patients were included, and a total of 68 radiosurgical interventions were delivered. Outcomes included the maintenance of pain relief assessed using Kaplan–Meier curves and treatment-related complications. Cox regression analyses were used to identify potential predictors of better pain relief. Results: Following the first radiosurgical treatments, the initial pain relief rate was 86% after a median latency period of 14 days. Adequate pain relief rates at 6, 12, 36 and 60 months were 86%, 52%, 35% and 24%, respectively. Adequate pain relief was sustained for an actuarial median of 12.7 months. After initial relief, pain recurrence occurred in 68% of patients. No statistical difference was seen in the duration of pain relief after initial or repeat radiosurgery ( p = 0.368). The most frequent complication was facial hypesthesia (Barrow Neurological Institute facial hypesthesia scale grade II: 10%; III: 6%; IV: 0%). Ipsilateral vascular compression was predictive of better efficacy ( p = 0.024). Conclusion: Radiosurgery for TN in patients with MS appears to be safe and to provide effective pain relief. Notably, radiological identification of vascular compression may predict more sustained pain relief.

Background: CyberKnife radiosurgery (RS), as an initial first treatment, is recognized as an efficient and safe modality for trigeminal neuralgia (TN). However, knowledge on repeat CyberKnife RS in refractory cases is limited. The objective was to evaluate the clinical outcomes of repeat CyberKnife RS for TN.Methods: A retrospective review of 33 patients with refractory TN treated a second time with CyberKnife RS from 2009 to 2021. The median follow-up period after the second RS was 26.0 months (range 0.3–115.8). The median dose for the repeat RS was 60 Gy (range 60.0–70.0). Pain relief after the intervention was assessed using the Barrow Neurological Institute scale for pain (I–V). Scores I to IIIb were classified as an adequate pain relief and scores IV–V were classified as a treatment failureResults: After the second RS, initial adequate pain relief was achieved in 87.9% of cases. The actuarial probabilities of maintaining an adequate pain relief at 6, 12, 24, and 36 months were 92.1%, 74.0%, 58.2%, and 58.2%, respectively. Regarding sustained pain relief, there was no significant difference between the first and the second RS. Sensory toxicity after the first RS was predictive of a better outcome following the second RS. The onset of hypesthesia rate was the same after the first or the second RS (21%).Conclusion: Repeat RS is an effective and safe method for the treatment of refractory TN.