Tag: Chronic pain

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Hybrid fluoroscopy–neuronavigation technique for percutaneous balloon compression in trigeminal neuralgia

Acta Neurochirurgica (2026) 168:110

This article presents a hybrid fluoroscopy–electromagnetic neuronavigation technique for percutaneous balloon compression in trigeminal neuralgia, detailing preoperative CT trajectory planning, intraoperative dual guidance, and practical steps to optimize foramen ovale cannulation. Emphasis is placed on safety measures, anesthesia considerations, and procedural specifics such as entry point, stylet use, and balloon inflation parameters.

The manuscript discusses candidate selection, advantages for elderly or comorbid patients, limitations including equipment needs and limited evidence, and practical tips to minimize complications. Key points summarize indications, procedural timing, anatomical landmarks, and the hybrid approach’s potential to shorten the learning curve for junior surgeons.

Purpose: Hybrid fluoroscopy + electromagnetic neuronavigation improves accuracy and safety of foramen ovale cannulation for percutaneous balloon compression in trigeminal neuralgia, reducing multiple passes in anatomically variable cases

Planning: Preoperative thin-slice CT is used to design an individualized needle trajectory to the foramen ovale, sometimes modifying the classical Hartel entry point to avoid bony collision

Anesthesia: Performed under general anesthesia because trigeminal ganglion manipulation can trigger a vagal reflex causing severe bradycardia/asystole; atropine readiness is required

Setup & entry: Patient supine with slight head extension; entry point is typically ~2.5 cm lateral to the oral commissure, with neuronavigation confirming the skin site/trajectory and C-arm fluoroscopy providing real-time position checks

Needle guidance: Needle advanced under fluoroscopy toward the petrous ridge–clivus junction (lateral view alignment), then an electromagnetic sensor/stylet is inserted to confirm and fine-tune alignment with the preplanned path before FO passage

Balloon step: After cannulation, a 4F Fogarty balloon is inflated with ~0.75 ml iopamidol to achieve the characteristic pear-shaped configuration under fluoroscopy

Compression time: Balloon compression is maintained for ~1–3 minutes to balance pain relief with risks such as hypoesthesia and masticatory weakness; limit to a maximum of 3 minutes

Clinical role & limits: Useful for medication-refractory TN, especially elderly/comorbid patients or when MRI shows no neurovascular conflict; limitations include added cost/skill needs and low evidence base (lack of randomized trials)

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A Scoping Review of Focused Ultrasound- Blood-Brain Barrier Opening for Treatment of Chronic Pain

Neurosurgery 98:328–338, 2026

This scoping review evaluates focused ultrasound–mediated blood–brain barrier opening (FUS‑BBBO) as a targeted drug‑delivery strategy to treat chronic pain, summarizing systematic literature screening and preclinical evidence. It outlines how FUS parameters, microbubbles, and regional targeting can transiently permit delivery of drugs and particles otherwise excluded by the BBB, potentially improving efficacy and reducing systemic toxicity.

The document surveys candidate therapeutics (opioids, peptides, antibodies, gene therapies) and particle vehicles (nanoparticles, liposomes, niosomes, AAVs), highlights preclinical successes and delivery challenges, and stresses safety, parameter optimization, and the need for human trials. It concludes that FUS‑BBBO combined with advanced delivery platforms holds promise but requires systematic clinical evaluation.

Blood-brain barrier (BBB) challenge: The BBB restricts most drugs from entering the brain, impeding effective pharmacological treatment of chronic pain, with only small, lipophilic molecules (<400–500 Da) able to cross easily, while 98% of small molecules and nearly all large molecules are excluded.

Focused ultrasound (FUS)-mediated BBB opening (FUSBO): FUSBO uses low-intensity ultrasound and microbubbles to temporarily, noninvasively open the BBB, enabling targeted drug delivery to specific brain regions without thermal damage.

Current pain therapies’ limitations: Opioids, gabapentin, cannabinoids, and other agents have limited efficacy and significant systemic side effects due to poor BBB penetration and susceptibility to efflux mechanisms like p-glycoprotein pumps.

Preclinical evidence, lack of human trials: While FUSBO has shown success in animal models for delivering pain therapies directly to the CNS and enhancing efficacy, no human studies have yet assessed FUSBO for chronic pain treatment.

Advancements in drug delivery particles: Nanoparticles, niosomes, polymeric nanoparticles, gold nanoparticles, and liposomes can be engineered to carry drugs across the BBB, improve bioavailability, and reduce toxicity, especially when combined with FUSBO.

Potential for biologics and gene therapy: FUSBO may enable delivery of monoclonal antibodies, single-chain fragment variable antibodies, and adeno-associated virus (AAV) gene therapies to the CNS, overcoming size and immune barriers.

Safety and technical considerations: FUSBO is generally safe in animal and early human studies, but potential risks include microglial activation, microhemorrhage, and neuronal suppression at high intensities; optimal parameters for various drugs and delivery systems remain to be established.

Outlook and clinical promise: FUSBO combined with advanced drug delivery particles could transform chronic pain management by bypassing the BBB, expanding the range of usable therapies, and improving the therapeutic window, but clinical trials are needed to confirm efficacy and safety in humans.

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Long-term outcomes of peripheral nerve field stimulation in patients with refractory trigeminal neuralgia: a cohort study

J Neurosurg 143:982–986, 2025

Peripheral nerve field stimulation (PNFS) for refractory trigeminal neuralgia showed high long-term treatment failure, especially in females, with frequent complications and revisions. Only half of male patients reported lasting benefit. PNFS should be considered cautiously for this condition.

Peripheral nerve field stimulation (PNFS) was studied for refractory trigeminal neuralgia with a long-term follow-up.

Fifteen patients (6 male, 9 female; median age 70) were included, with a median follow-up of 93 months.

PNFS had a high rate of long-term treatment failure, especially in females.

The median time to treatment failure was 2 years (5.1 years in males, 1.5 years in females; p = 0.003).

Only 3 patients (all male) reported ongoing benefit.

Complications and revision surgeries were common (4 patients, 7 revisions).

No significant differences in outcomes were found between classic and secondary trigeminal neuralgia or by patient age.

PNFS should be considered cautiously due to limited long-term efficacy and frequent complications.

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Bilateral focused ultrasound medial thalamotomies for trigeminal neuropathic pain: a randomized controlled study

J Neurosurg 140:1799–1809, 2024

Medial thalamotomy has been shown to benefit patients with neuropathic pain, but widespread adoption of this procedure has been limited by reporting of clinical outcomes in studies without a control group. This study aimed to minimize confounders associated with medial thalamotomy for treating chronic pain by using modern MRI-guided stereotactic lesioning and a rigorous clinical design.

METHODS This prospective, double-blinded, randomized controlled trial in 10 patients with trigeminal neuropathic pain used sham procedures as controls. Participants underwent assessments by a pain psychologist and pain management clinician, including use of the following measures: the Numeric Pain Rating Scale (NPRS); patient-reported outcome measures; and patient’s impression of improvement at baseline, 1 day, 1 week, 1 month, and 3 months postprocedure. Patients in the treated group underwent bilateral focused ultrasound (FUS) medial thalamotomy targeting the central lateral nucleus. Patients in the control group underwent sham procedures with energy output disabled. The primary efficacy outcome measure was between-group differences in pain intensity (using the NPRS) at baseline and at 3 months postprocedure. Adverse events were measured for safety and included MRI analysis. Exploratory measures of connectivity and metabolism were analyzed using diffusion tensor imaging, functional MRI, and PET, respectively.

RESULTS There were no serious complications from the FUS procedures. MRI confirmed bilateral medial thalamic ablations. There was no significant improvement in pain intensity from baseline to 3 months, either for patients undergoing FUS medial thalamotomy or for sham controls; and the between-group change in NPRS score as the primary efficacy outcome measure was not significantly different. Patient-reported outcome assessments demonstrated improvement (i.e., a decrease) only in pain interference with enjoyment of life at 3 months. There was a perception of benefit at 1 week, but only for patients treated with FUS and not for the sham cohort. Advanced neuroimaging showed that these medial thalamic lesions altered structural connectivity with the postcentral gyrus and demonstrated a trend toward hypometabolism in the insula and amygdala.

CONCLUSIONS This randomized controlled trial of bilateral FUS medial thalamotomy did not reduce the intensity of trigeminal neuropathic pain, although it should be noted that the ability to estimate the magnitude of treatment effects is limited by the small cohort.

Clinical trial registration no.: NCT03309813 (ClinicalTrials.gov)

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Focused Ultrasound Central Lateral Thalamotomy for the Treatment of Refractory Neuropathic Pain

Neurosurgery 94:690–699, 2024

Magnetic resonance–guided focused ultrasound (MRgFUS) central lateral thalamotomy (CLT) has not yet been validated for treating refractory neuropathic pain (NP). Our aim was to assess the safety and potential efficacy of MRgFUS CLT for refractory NP.

METHODS: In this prospective, nonrandomized, single-arm, investigator-initiated phase I trial, patients with NP for more than 6 months related to phantom limb pain, spinal cord injury, or radiculopathy/radicular injury and who had undergone at least one previous failed intervention were eligible. The main outcomes were safety profile and pain as assessed using the brief pain inventory, the pain disability index, and the numeric rating scale. Medication use and the functional connectivity of the default mode network (DMN) were also assessed.

RESULTS: Ten patients were enrolled, with nine achieving successful ablation. There were no serious adverse events and 12 mild/moderate severity events. The mean age was 50.9 years (SD: 12.7), and the mean symptom duration was 12.3 years (SD: 9.7). Among eight patients with a 1-year follow-up, the brief pain inventory decreased from 7.6 (SD: 1.1) to 3.8 (SD: 2.8), with a mean percent decrease of 46.3 (SD: 40.6) (paired t-test, P = .017). The mean pain disability index decreased from 43.0 (SD: 7.5) to 25.8 (SD: 16.8), with a mean percent decrease of 39.3 (SD: 41.6) (P = .034). Numeric rating scale scores decreased from a mean of 7.2 (SD: 1.8) to 4.0 (SD: 2.8), with a mean percent decrease of 42.8 (SD: 37.8) (P = .024). Patients with predominantly intermittent pain or with allodynia responded better than patients with continuous pain or without allodynia, respectively. Some patients decreased medication use. Resting-state functional connectivity changes were noted, from disruption of the DMN at baseline to reactivation of connectivity between DMN nodes at 3 months.

CONCLUSION: MRgFUS CLT is feasible and safe for refractory NP and has potential utility in reducing symptoms as measured by validated pain scales.

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Somatosensory functional MRI tractography for individualized targeting of deep brain stimulation in patients with chronic pain after brachial plexus injury

Acta Neurochirurgica (2019) 161:2485–2490

The optimal targets for deep brain stimulation (DBS) in patients with refractory chronic pain are not clearly defined. We applied sensory functional MRI (fMRI)- and diffusion tensor imaging (DTI)-based DBS in chronic pain patients into 3 different targets to ascertain the most beneficial individual stimulation site.

Methods Three patients with incapacitating chronic pain underwent DBS into 3 targets (periventricular gray (PVG), ventroposterolateral thalamus (VPL), and posterior limb of the internal capsule according to fMRI and DTI (PLIC). The electrodes were externalized and double-blinded tested for several days. Finally, the two electrodes with the best pain reduction were kept for permanent stimulation. The patients were then followed up for 12 months. Outcome measures comprised the numerical rating scale (NRS), short-form McGill’s score (SF-MPQ), and health-related quality of life (SF-36).

Results Continuous pain (mean NRS 6.6) was reduced to NRS 3.6 after 12 months. Only with stimulation of the PLIC pain attacks, that occurred at least 3 times a week (mean NRS 9.6) resolved in 2 patients and improved in one patient concerning both intensity (NRS 5) and frequency (twice a month). The mean SF-MPQ decreased from 92.7 to 50. The health-related quality of life improved considerably.

Conclusion fMRI- and DTI-based DBS to the PLIC was the only target with a significant effect on pain attacks and seems to be the most promising target in chronic pain patients after brachial plexus injury. The combination with PVG or VPL can further improve patients’ outcome especially in terms of reducing the continuous pain.

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Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain

spinal-cord-stimulation-for-the-treatment-of-chronic-back-and-leg-pain

Neurosurgery 79:667–677, 201

Pain relief with spinal cord stimulation (SCS) has focused historically on paresthesias overlapping chronically painful areas. A higher level evidence supports the use of SCS in treating leg pain than supports back pain, as it is difficult to achieve adequate paresthesia coverage, and then pain relief, in the low back region. In comparison, 10-kHz high-frequency (HF10 therapy) SCS therapy does not rely on intraoperative paresthesia mapping and remains paresthesia-free during therapy. OBJECTIVE: To compare long-term results of HF10 therapy and traditional lowfrequency SCS.

METHODS: A pragmatic randomized, controlled, pivotal trial with 24-month follow-up was conducted across 11 comprehensive pain treatment centers. Subjects had Visual Analog Scale scores of$5.0/10.0 cmfor both back and leg pain, and were assigned randomly (1:1) to receive HF10 therapy or low-frequency SCS. The primary end point was a responder rate, defined as $50% back pain reduction from baseline at 3 months with a secondary end point at 12 months (previously reported). In this article, 24-month secondary results are presented. Non-inferiority was first assessed, and if demonstrated the results were tested for superiority.

RESULTS: In the study, 198 subjects were randomized (101 HF10 therapy, 97 traditional SCS). One hundred seventy-one subjects (90 HF10 therapy, 81 traditional SCS) successfully completed a short-term trial and were implanted. Subjects averaged 54.96 12.9 years old, 13.6 6 11.3 years since diagnosis, 86.6% had back surgery, 88.3% were taking opioid analgesics. At 3 months, 84.5% of implanted HF10 therapy subjects were responders for back pain and 83.1% for leg pain, and 43.8% of traditional SCS subjects were responders for back pain and 55.5% for leg pain (P , .001 for both back and leg pain comparisons, noninferiority and superiority). At 24 months, more subjects were responders to HF10 therapy than traditional SCS (back pain: 76.5% vs 49.3%; 27.2% difference, 95% CI, 10.1%-41.8%; P, .001 for non-inferiority and superiority; leg pain: 72.9% vs 49.3%; 23.6% difference, 95% CI, 5.9%-38.6%; P , .001 for non-inferiority and P = .003 for superiority). Also at 24 months, back pain decreased to a greater degree with HF10 therapy (66.9% 6 31.8%) than traditional SCS (41.1% 6 36.8%, P , .001 for non-inferiority and superiority). Leg pain also decreased to a greater degree with HF10 therapy (65.1% 6 36.0%) than traditional SCS (46.0% 6 40.4%, P , .001 for non-inferiority and P = .002 for superiority).

CONCLUSION: This study demonstrates long-term superiority of HF10 therapy compared with traditional SCS in treating both back and leg pain. The advantages of HF10 therapy are anticipated to impact the management of chronic pain patients substantially.

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Invasive Motor Cortex Stimulation for Trigeminal Facial Neuropathic Pain Syndromes

clinical_significance_of_invasive_motor_cortex

Neurosurgery 79:655–666, 2016

Invasive neuromodulation of the cortical surface for various chronic pain syndromes has been performed for .20 years. The significance of motor cortex stimulation (MCS) in chronic trigeminal neuropathic pain (TNP) syndromes remains unclear. Different techniques are performed worldwide in regard to operative procedure, stimulation parameters, test trials, and implanted materials.

OBJECTIVE: To present the clinical experiences of a single center with MCS, surgical approach, complications, and follow-up as a prospective, noncontrolled clinical trial.

METHODS: The implantation of epidural leads over the motor cortex was performed via a burr hole technique with neuronavigation and intraoperative neurostimulation. Special focus was placed on a standardized test trial with an external stimulation device and the implementation of a double-blinded or placebo test phase to identify falsepositive responders.

RESULTS: A total of 36 patients with TNP were operated on, and MCS was performed. In 26 of the 36 patients (72%), a significant pain reduction from a mean of 8.11 to 4.58 (on the visual analog scale) during the test trial was achieved (P , .05). Six patients were identified as false-positive responders (17%). At the last available follow-up of 26 patients (mean, 5.6 years), active MCS led to a significant pain reduction compared with the preoperative pain ratings (mean visual analog scale score, 5.01; P , .05).

CONCLUSION: MCS is an additional therapeutic option for patients with refractory chronic TNP, and significant long-term pain suppression can be achieved. Placebo or double-blinded testing is mandatory.

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Epidural spinal cord stimulation for neuropathic pain

Spinal_Cord_Stimulation_Devices_clip_image010

Acta Neurochir (2015) 157:739–741

Spinal cord stimulation (SCS) is a technique used worldwide to treat several types of chronic neuropathic pain refractory to any conservative treatment. The aim of this data collection is to enforce evidence of SCS effectiveness on neuropathic chronic pain reported in the literature and to speculate on the usefulness of the trial period in determining the long–term efficacy. Moreover, the very low percentage of undesired side effects and complications reported in our case series suggests that all implants should be performed by similarly well-trained and experienced professionals.

Method A multicentric data collection on a common database from 11 Italian neurosurgical departments started 3years ago. Two different types of electrodes (paddle or percutaneous leads) were used. Of 122 patients, 73 % (N=89) were submitted to a trial period, while the remaining patients underwent the immediate permanent implant (N=33). Statistical comparisons of continuous variables between groups were performed.

Results Most of the patients (80 %) had predominant pain to their lower limbs, while only 17 % of patients had prevalent axial pain. Significant reduction in pain, as measured by variation in visual analogue scale (VAS) score, was observed at least 1 year after implantation in 63.8%of the cases, 59.5%of patients who underwent a test trial and 71.4% of patients who underwent permanent implant at once. No statistical differences were found between the lower-limb pain group and the axial pain group.

Conclusions No relevant differences in long-term outcomes were observed in previously tested patients compared with patients implanted at once. Through this analysis we hope to recruit new centres, to give more scientific value to our results.

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