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.

Long-Term Results of Cortical Motor Stimulation for Neuropathic Peripheral and Central Pain: Real-World Evidence From Two Independent Centers

Neurosurgery 94:147–153, 2024

Cortical motor stimulation (CMS) is used to modulate neuropathic pain. The literature supports its use; however, short follow-up studies might overestimate its real effect. This study brings real-world evidence from two independent centers about CMS methodology and its long-term outcomes.

METHODS: Patients with chronic refractory neuropathic pain were implanted with CMS. The International Classification of Headache Disorders 3rd Edition was used to classify craniofacial pain and the Douleur Neuropathique en 4 Questions Scale score to explore its neuropathic nature. Demographics and clinical and surgical data were collected. Pain intensity at 6, 12, and 24 months and last follow-up was registered. Numeric rating scale reduction of ≥50% was considered a good response. The Clinical Global Impression of Change scale was used to report patient satisfaction.

RESULTS: Twelve males (38.7%) and 19 females (61.3%) with a mean age of 55.8 years (±11.9) were analyzed. Nineteen (61.5%) were diagnosed from painful trigeminal neuropathy (PTN), and seven (22.5%) from central poststroke pain. The mean follow-up was 51 months (±23). At 6 months, 42% (13/31) of the patients were responders, all of them being PTN (13/19; 68.4%). At last follow-up, only 35% (11/31) remained responders (11/19 PTN; 58%). At last follow-up, the global Numeric rating scale reduction was 34% (P= .0001). The Clinical Global Impression of Change scale punctuated 2.39 (±0.94) after 3 months from the surgery and 2.95 (±1.32) at last follow-up (P= .0079). Signs of suspicious placebo effect were appreciated in around 40% of the nonresponders.

CONCLUSION: CMS might show long-term efficacy for neuropathic pain syndromes, with the effect on PTN being more robust in the long term. Multicentric clinical trials are needed to confirm the efficacy of this therapy for this and other conditions.

Positioning of epidural electrode for motor cortex stimulation in general anesthesia based on intraoperative electrophysiological monitoring to treat refractory trigeminal neuropathic pain

Acta Neurochirurgica (2023) 165:3403–3407

Motor cortex stimulation (MCS) represents a treatment option for refractory trigeminal neuralgia (TGN). Usually, patients need to be awake during surgery to confirm a correct position of the epidural electrode above the motor cortex, reducing patient’s comfort.

Method Epidural cortical mapping (ECM) and motor evoked potentials (MEPs) were intraoperatively performed for correct localization of motor cortex under general anesthesia that provided comparable results to test stimulation after letting the patient to be awake during the operation.

Conclusion Intraoperative ECM and MEPs facilitate a confirmation of correct MCS-electrode position above the motor cortex allowing the MCS-procedure to be performed under general anesthesia.

Gamma Knife Central Lateral Thalamotomy for Chronic Neuropathic Pain

Neurosurgery 92:363–369, 2023

Chronic neuropathic pain can be severely disabling and is difficult to treat. The medial thalamus is believed to be involved in the processing of the affectivemotivational dimension of pain, and lesioning of the medial thalamus has been used as a potential treatment for neuropathic pain. Within the medial thalamus, the central lateral nucleus has been considered as a target for stereotactic lesioning.

OBJECTIVE: To study the safety and efficacy of central lateral thalamotomy using Gamma Knife radiosurgery (GKRS) for the treatment of neuropathic pain.

METHODS: We retrospectively reviewed all patients with neuropathic pain who underwent central lateral thalamotomy using GKRS. We report on patient outcomes, including changes in pain scores using the Numeric Pain Rating Scale and Barrow Neurological Institute pain intensity score, and adverse events.

RESULTS: Twenty-one patients underwent central lateral thalamotomy using GKRS between 2014 and 2021. Meaningful pain reduction occurred in 12 patients (57%) after a median period of 3 months and persisted in 7 patients (33%) at the last follow-up (the median follow-up was 28 months). Rates of pain reduction at 1, 2, 3, and 5 years were 48%, 48%, 19%, and 19%, respectively. Meaningful pain reduction occurred more frequently in patients with trigeminal deafferentation pain compared with all other patients (P = .009). No patient had treatment-related adverse events.

CONCLUSION: Central lateral thalamotomy using GKRS is remarkably safe. Pain reduction after this procedure occurs in a subset of patients and is more frequent in those with trigeminal deafferentation pain; however, pain recurs frequently over time.


Brain Structural Changes in Carpal Tunnel Syndrome Patients

Neurosurgery 89:978–986, 2021

Carpal tunnel syndrome (CTS) is a common peripheral entrapment neuropathy. However, CTS-related changes of brain structural covariance and structural covariance networks (SCNs) patterns have not been clearly studied. OBJECTIVE: To explore CTS-related brain changes from perspectives of structural connectivity and SCNs.

METHODS: Brain structural magnetic resonance images were acquired from 27 CTS patients and 19 healthy controls (HCs). Structural covariance and SCNs were constructed based on gray matter volume. The global network properties including clustering coefficient (Cp), characteristic path length (Lp), small-worldness index, global efficiency (Eglob), and local efficiency (Eloc) and regional network properties including degree, betweenness centrality (BC), and Eloc of a given node were calculated with graph theoretical analysis.

RESULTS: Compared with HCs, the strength of structural connectivity between the dorsal anterior insula and medial prefrontal thalamus decreased (P < .001) in CTS patients. There was no intergroup difference of area under the curve for Cp, Lp¸Eglob, and Eloc (all P>.05). The real-world SCN of CTS patients showed a small-world topology ranging from 2% to 32%. CTS patients showed lower nodal degrees of the dorsal anterior insula and medial prefrontal thalamus, and higher Eloc of a given node and BC in the lateral occipital cortex (P < .001) and the dorsolateral middle temporal gyrus (P < .001) than HCs, respectively.

CONCLUSION: CTS had a profound impact on brain structures from perspectives of structural connectivity and SCNs.

Gamma Knife central lateral thalamotomy for the treatment of neuropathic pain

J Neurosurg 135:228–236, 2021

The goal of this study was to assess the safety and efficacy of stereotactic central lateral thalamotomy with Gamma Knife radiosurgery in patients with neuropathic pain.

METHODS Clinical and radiosurgical data were prospectively collected and analyzed in patients with neuropathic pain who underwent Gamma Knife central lateral thalamotomy. The safety and efficacy of the lesioning procedure were evaluated by neurological examination and standardized scales for pain intensity and health-related quality of life. Visual analog scale (VAS) for pain, McGill Pain Questionnaire (MPQ), EuroQol–5 dimensions (EQ-5D), and the 36-Item Short Form Health Survey, version 2 (SF-36v2) were measured during baseline and postoperative follow-up evaluations at 3, 6, 12, 24, and 36 months.

RESULTS Eight patients with neuropathic pain underwent Gamma Knife central lateral thalamotomy. Four patients suffered from trigeminal deafferentation pain, 2 from brachial plexus injury, 1 from central poststroke facial neuropathic pain, and 1 from postherpetic neuralgia. No lesioning-related adverse effect was recorded during the follow-up periods. All patients had pain reduction following thalamotomy. The mean follow-up time was 24 months. At the last follow-up visits, 5 patients reported ≥ 50% VAS pain reduction. The overall mean VAS pain score was 9.4 (range 8–10) before radiosurgery. After 1 year, the mean VAS pain score decreased significantly, from 9.4 (range 8–10) to 5.5 (mean -41.33%, p = 0.01). MPQ scores significantly decreased (mean -22.18%, p = 0.014). Statistically significant improvements of the SF-36v2 quality of life survey (mean +48.16%, p = 0.012) and EQ-5D (+45.16%, p = 0.012) were observed. At 2 years after radiosurgery, the VAS pain score remained significantly reduced to a mean value of 5.5 (p = 0.027). Statistically significant improvements were also observed for the MPQ (mean -16.05%, p = 0.034); the EQ-5D (mean +35.48%, p = 0.028); and the SF-36v2 (mean +35.84%, p = 0.043). At the last follow-up visits, pain had recurred in 2 patients, who were suffering from central poststroke neuropathic pain and brachial plexus injury, respectively.

CONCLUSIONS Safe, nonpharmacological therapies are imperative for the management of refectory chronic pain conditions. The present series demonstrates that Gamma Knife central lateral thalamotomy is safe and potentially effective in the long term for relieving chronic neuropathic pain refractory to pharmacotherapy and for restoring quality of life.


Dorsal anterior cingulate cortex (ACC) deep brain stimulation (DBS): a promising surgical option for the treatment of refractory thalamic pain syndrome (TPS)

Acta Neurochirurgica (2019) 161:1579–1588

Neuroimaging evidences and previous successful case series of cingulotomy for cancer pain have disclosed the key- role of the dorsal anterior cingulate cortex (ACC) in the generation of the empathic and affective dimension of pain. The aim of this study is to assess the effectiveness and safety of ACC neuromodulation for the treatment of the thalamic pain syndrome (TPS), a chronic neuropathic disease often complicated by severe affective and emotional distress in the long term.

Method From January 2015 to April 2017, 5 patients with pure drug-refractory TPS underwent ACC deep brain stimulation (DBS) at our institution. Quantitative assessment of pain and health-related quality of life were performed 1 day before surgery and postoperatively at 6 and 18 months by using the numeric rating scale (NRS), the 36-item short-form health survey (SF-36), and the McGill pain and the EuroQol5-domain questionnaires.

Results Mean age at surgery was 56.2 years (range, 47–66). NRS score improved by 37.9% at 6 months (range, − 22.2 to − 80%) and by 35% at 18 months (range, − 11.1 to − 80%). At the last follow-up, one patient reported a relevant pain reduction (NRS 2), only complaining of mild pain poorly interfering with activities of daily living. Concomitant improvements in the McGill and EuroQol5-domain pain questionnaires, SF-36 total and sub-item scores were also noticed at each follow-up. No surgical or stimulation-related complications occurred during the study period.

Conclusions ACC DBS may be a safe and promising surgical option to alleviate discomfort and improve the overall quality of life in a patient affected by drug-resistant TPS. Further prospective, larger, and randomized studies are needed to validate these findings.

Efficacy of deep rTMS for neuropathic pain in the lower limb: a randomized, double-blind crossover trial of an H-coil and figure-8 coil

J Neurosurg 127:1172–1180, 2017

Electrical motor cortex stimulation can relieve neuropathic pain (NP), but its use requires patients to undergo an invasive procedure. Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) using a figure-8 coil can relieve NP noninvasively, but its ability to relieve lower limb pain is still limited. Deep rTMS using an H-coil can effectively stimulate deep brain regions and has been widely used for the treatment of various neurological diseases; however, there have been no clinical studies comparing the effectiveness of figure-8 coils and H-coils. This study assessed the clinical effectiveness of 5 once-daily stimulations with H-coils and figure-8 coils in patients with NP.

METHODS This randomized, double-blind, 3-way crossover trial examined 18 patients with NP who sequentially received 3 types of stimulations in the M1 for 5 consecutive days; each 5-day stimulation period was followed by a 17-day follow-up period before crossing over to the next type of stimulation. During each rTMS session, patients received a 5-Hz rTMS to the M1 region corresponding to the painful lower limb. The visual analog scale (VAS) and the Japanese version of the short-form McGill Pain Questionnaire 2 (SF-MPQ2-J) were used to measure pain intensity. The primary outcome was VAS score reduction immediately after and 1 hour after intervention.

RESULTS Both the VAS and SF-MPQ2-J showed significant pain improvement immediately after deep rTMS with an H-coil as compared with the sham group (p < 0.001 and p = 0.049, respectively). However, neither outcome measure showed significant pain improvement when using a figure-8 coil. The VAS also showed significant pain improvement 1 hour after deep rTMS with an H-coil (p = 0.004) but not 1 hour after rTMS using a figure-8 coil. None of the patients exhibited any serious adverse events.

CONCLUSIONS The current findings suggest that the use of deep rTMS with an H-coil in the lower limb region of the M1 in patients with NP was tolerable and could provide significant short-term pain relief.

Clinical trial registration no.: UMIN000010536 (


Motor cortex stimulation and neuropathic pain: how does motor cortex stimulation affect pain-signaling pathways?

Motor cortex stimulation and neuropathic pain- how does motor cortex stimulation affect pain-signaling pathways?

J Neurosurg 124:866–876, 2016

Neuropathic pain is often severe. Motor cortex stimulation (MCS) is used for alleviating neuropathic pain, but the mechanism of action is still unclear. This study aimed to understand the mechanism of action of MCS by investigating pain-signaling pathways, with the expectation that MCS would regulate both descending and ascending pathways.

Methods Neuropathic pain was induced in Sprague-Dawley rats. Surface electrodes for MCS were implanted in the rats. Tactile allodynia was measured by behavioral testing to determine the effect of MCS. For the pathway study, immunohistochemistry was performed to investigate changes in c-fos and serotonin expression; micro–positron emission tomography (mPET) scanning was performed to investigate changes of glucose uptake; and extracellular electrophysiological recordings were performed to demonstrate brain activity.

Results MCS was found to modulate c-fos and serotonin expression. In the mPET study, altered brain activity was observed in the striatum, thalamic area, and cerebellum. In the electrophysiological study, neuronal activity was increased by mechanical stimulation and suppressed by MCS. After elimination of artifacts, neuronal activity was demonstrated in the ventral posterolateral nucleus (VPL) during electrical stimulation. This neuronal activity was effectively suppressed by MCS.

Conclusions This study demonstrated that MCS effectively attenuated neuropathic pain. MCS modulated ascending and descending pain pathways. It regulated neuropathic pain by affecting the striatum, periaqueductal gray, cerebellum, and thalamic area, which are thought to regulate the descending pathway. MCS also appeared to suppress activation of the VPL, which is part of the ascending pathway.

Epidural spinal cord stimulation for neuropathic pain


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.

Subdural motor cortex stimulation

Subdural motor cortex stimulation

Acta Neurochir (2014) 156:2289–2294

Motor cortex stimulation (MCS) is considered to be an effective treatment in some types of chronic refractory neuropathic pain. The aim of this study is to evaluate and confirm the feasibility, efficacy and security of our surgical technique for subdural motor cortex stimulation (SDMCS) on 18 consecutive cases with follow-up of at least 3 years.

Methods Our population consists of 18 consecutive patients (12male) between 2000 and 2010,with a mean age of 63 years (11–91). The mean follow-up was 86 months (20–140 months). We identified the central sulcus by using classical anatomic landmarks and neuronavigation (BrainLab system; BrainLAB, Inc., Redwood City, CA). An elongated craniotomy (3 cm in length, 1 cm in width)was performed followed by linear opening of the dura mater. An eight-polar plate electrode (Specify Lead, 3998;Medtronic,Minneapolis,MN) was then slipped smoothly through this linear opening. In patients with interhemispheric electrodes (patients 2 and 17), we performed a parasagittal craniotomy of 4 cm length and 2 cm width.

Results At last follow-up assessment, 14 patients had a favourable outcome (77.7 %): 10 patients with excellent relief of pain (>80 %), 1 with good relief of pain (60–80 %) and 3 with satisfactory relief of pain (50–60 %). Four patients showed bad results (<50 %). We did not observe any late complications specific to SD MCS.

Conclusion We report an efficacy at least as good as ED MCS, with no complications specific to SD MCS, even with prolonged follow-up. The data are insufficient to actually prove a lower energy use in SD MCS.

Keywords Neuropathic pain , Neurostimulation , Motor cortex stimulation, Subdural

Deep Brain Stimulation of the Anterior Cingulate Cortex

Anterior cingulate DBS

Neurosurgery 74:628–637, 2014

Deep brain stimulation (DBS) has shown considerable promise for relieving nociceptive and neuropathic symptoms of refractory chronic pain. Nevertheless, for some patients, standard DBS for pain remains poorly efficacious. Pain is a multidimensional experience with an affective component: the unpleasantness. The anterior cingulate cortex (ACC) is a structure involved in this affective component, and targeting it may relieve patients’ pain.

OBJECTIVE: To describe the first case series of ACC DBS to relieve the affective component of chronic neuropathic pain.

METHODS: Sixteen patients (13 male and 3 female patients) with neuropathic pain underwent bilateral ACC DBS. The mean age at surgery was 48.7 years (range, 33-63 years). Patient-reported outcome measures were collected before and after surgery using a Visual Analog Scale, SF-36 quality of life survey, McGill Pain Questionnaire, and EQ-5D (EQ-5D and EQ-5D Health State) questionnaires.

RESULTS: Fifteen patients (93.3%) transitioned from externalized to fully internalized systems. Eleven patients had data to be analyzed with a mean follow-up of 13.2 months. Post-surgery, the Visual Analog Scale score dropped below 4 for 5 of the patients, with 1 patient free of pain. Highly significant improvement on the EQ-5D was observed (mean, 120.3%; range, 10%-183%; P = .008). Moreover, statistically significant improvements were observed for the physical functioning and bodily pain domains of the SF-36 qualityof- life survey: mean, 164.7% (range, 28.9%-1276%; P = .015) and mean 139.0% (range, 233.8%-1159%; P = .050), respectively.

CONCLUSION: Affective ACC DBS can relieve chronic neuropathic pain refractory to pharmacotherapy and restore quality of life.

Multicolumn Spinal Cord Stimulation Lead Implantation Using an Optic Transligamentar Minimally Invasive Technique


Neurosurgery 73:550–553, 2013 

A new generation of neurostimulation surgical leads is used to increase the success of spinal cord stimulation in difficult-to-treat indications such as failed back surgery syndrome. Minimal access spinal technologies (MASTs) have previously been used for surgical lead implantation. However, only a unilateral approach was possible, causing difficulties for median lead placement, and not always preventing laminectomy. A recent MAST technique was used to implant spinal cord stimulation leads without these limitations.

OBJECTIVE: To describe the MAST technique used in a pilot study.

METHODS: Twenty-four consecutive patients were implanted with a multicolumn surgical lead for refractory chronic back and leg pain by using the optic transligamentar MAST technique.

RESULTS: The MAST technique allowed median lead placement, facilitated visualization of the spine, and permitted transligamentar insertion that minimized scarring and muscle damage. No technique-related adverse events or lead revisions were reported.

CONCLUSION: Use of a MAST approach could be useful in safe implantation of multicolumn surgical leads in difficult-to-treat, refractory lower back pain conditions such as failed back surgery syndrome.