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Introduction: Persistent spinal pain syndrome (PSPS) with predominant low-back pain (LBP) is difficult to manage when conservative and surgical treatments fail. Dorsal root ganglion stimulation (DRG-S) offers segmental, focal neuromodulation that may be particularly suited for managing axial LBP, yet long-term evidence from real-world practice remains limited. This study evaluated the effectiveness, safety, and impact on medication use of bilateral T12 DRG-S in patients with intractable LBP, using prospectively collected registry data.

Methods: Of 33 consecutive patients with chronic LBP assessed for DRG-S, 20 underwent trial stimulation after multidisciplinary evaluation. Eighteen (90%) proceeded to permanent implantation following ≥ 50% pain reduction during trial. Patients were followed via a digital platform at 3, 6, 12, and 24 months. Outcomes included pain intensity (NRS), quality of life (PROMIS-29), pain catastrophizing (PCS), satisfaction, medication use, and adverse events. Statistical comparisons were made between baseline and follow-up time points using paired tests.

Results: Pain intensity decreased substantially and significantly across all follow-up assessments: mean NRS declined from 8.0 ± 1.8 at baseline to 3.6 ± 1.6 at 3 months, 3.2 ± 1.8 at 6 months, 3.6 ± 1.7 at 12 months, and 2.9 ± 1.6 at 24 months (all p < 0.001). At 24 months, 100% of patients achieved ≥ 30% pain reduction and 70% achieved ≥ 50% reduction. Patient-reported outcomes demonstrated broad improvements. PROMIS-29 domains showed significant gains in physical function, pain interference, fatigue, and sleep disturbance, with consistent improvements also observed in anxiety and depression. Pain catastrophizing (PCS) scores decreased markedly, with total scores reduced by 47%–62% across follow-ups (all p < 0.001), reflecting improvements across helplessness, magnification, and rumination subdomains. Medication use declined over time. Mean opioid dose fell from 27 mg/day at baseline to 11.25 mg/day at 1 year and 4.44 mg/day at 2 years (p = 0.019 and 0.011, respectively). Paracetamol use also decreased significantly, whereas gabapentinoid use remained variable. Seven hardware-related complications were recorded (lead migration n = 3, lead fracture/damage n = 4), all successfully managed with revision surgery. Kaplan–Meier analysis estimated mean time to complication at 1080 days. Two patients discontinued therapy (EOT), both for reasons unrelated to device failure.

Conclusions: In this prospective registry, bilateral T12 DRG-S provided durable reduction in pain intensity, improved physical, psychosocial, and cognitive outcomes, and facilitated meaningful opioid-sparing effects over 2 years. Complications were limited to correctable hardware issues, and therapy discontinuation was rare. Although larger multicentre studies are warranted, these findings add important real-world evidence supporting DRG-S as a valuable therapeutic option for refractory axial LBP.

Background: subperception (paresthesia-free) dorsal root ganglion (DRG) stimulation is increasingly used for focal neuropathic pain, but sham-controlled evidence remains limited. We conducted a randomized, double-blind, sham-controlled crossover trial with enriched enrollment design in established DRG-stimulation responders.

Methods: In this single-center trial, adults with chronic peripheral neuropathic or nociplastic pain with implanted DRG system and sustained response (≥50% pain reduction for ≥3 months on stable stimulation settings and medication) were randomized 1:1 to active→sham or sham→active stimulation. Participants completed two 5-day treatment periods separated by a 24-hour washout with stimulation off. Active stimulation was delivered at 90% of the perception threshold, and sham was stimulation off. The primary outcome was median pain intensity on a 0–10 Numeric Rating Scale (NRS). Secondary outcomes included patient satisfaction and Patient Global Impression of Change (PGIC) domains. Analyses used Wilcoxon signed-rank tests with Hodges-Lehmann estimates.

Results: In 20 randomized patients, pain intensity was lower during active than sham stimulation (median NRS 3.0 (IQR 2.0–4.0) vs 6.0 (IQR 4.0–7.0); Hodges-Lehmann median difference, −2.5; 95% CI −3.0 to −2.0; p<0.001). Patient satisfaction and all PGIC domains favored active stimulation. Two participants terminated one treatment period early per prespecified criteria; available data were retained. No serious or device-related adverse events were reported.

INTRODUCTION: Pain, comprising sensory and emotional elements, is influenced by pain catastrophizing, which magnifies pain and promotes helplessness and rumination. This study explores the relationship between pain catastrophizing and outcomes following selective nerve root blockade (SNRB) in patients with lumbar radicular pain (LRP).

METHODS: A prospective cohort study of 103 LRP patients, confirmed by MRI, was conducted. All participants underwent SNRB at Umeå University Hospital. Outcomes were measured using PROMIS-29 and the Pain Catastrophizing Scale (PCS) at baseline and several intervals up to 84 days post-intervention. Patients were categorized into responder (≥30% pain reduction) and non-responder groups and stratified into three groups based on baseline PCS scores. Changes in outcomes from baseline to 14 days post-SNRB were analyzed in relation to PCS groups. PCS changes over time were evaluated between responders and non-responders. Statistical analyses assessed PCS and outcome changes.

RESULTS: Baseline pain catastrophizing was not a significant predictor of pain response to SNRB. However, responders demonstrated significant reductions in pain catastrophizing following the intervention, suggesting that SNRB may influence cognitive coping mechanisms related to pain.

CONCLUSION: SNRB reduces pain catastrophizing in LRP patients, although baseline catastrophizing does not predict pain outcomes. Addressing catastrophizing remains important but may serve better as an outcome measure rather than a predictor of treatment response.

While the effectiveness of deep brain stimulation in alleviating essential tremor is well-established, the underlying mechanisms of the treatment are unclear. Essential tremor, as characterized by tremor during action, is proposed to be driven by a dysfunction in the cerebello-thalamo-cerebral circuit that is evident not only during motor actions but also during rest. Stimulation effects on resting-state functional connectivity were investigated by functional MRI in 16 essential tremor patients with fully implanted deep brain stimulation in the caudal zona incerta during On-and-Off therapeutic stimulation, in a counterbalanced design. Functional connectivity was calculated between different constellations of sensorimotor as well as non-sensorimotor regions (as derived from seed-based and data-driven approaches), and compared between On and Off stimulation. We found that deep brain stimulation did not modulate resting-state functional connectivity. The lack of modulation by deep brain stimulation during resting-state, in combination with previously demonstrated effects on the cerebello-thalamo-cerebral circuit during motor tasks, suggests an action-dependent modulation of the stimulation in essential tremor.

Background: Long-term data on the effects of deep brain stimulation (DBS) for essential tremor (ET) is scarce, especially regarding DBS in the caudal Zona incerta (cZi) and the posterior subthalamic area (PSA). Objectives: The aim of this prospective study was to evaluate the effect of cZi/PSA DBS in ET at 10 years after surgery.

Methods: Thirty-four patients were included. All patients received cZi/PSA DBS (5 bilateral/29 unilateral) and were evaluated at regular intervals using the essential tremor rating scale (ETRS).

Results: One year after surgery, there was a 66.4% improvement of total ETRS and 70.7% improvement of tremor (items 1–9) compared with the preoperative baseline. Ten years after surgery, 14 patients had died and 3 were lost to follow-up. In the remaining 17 patients, a significant improvement was maintained (50.8% for total ETRS and 55.8% for tremor items). On the treated side the scores of hand function (items 11–14) had improved by 82.6% at 1 year after surgery, and by 66.1% after 10 years. Since off-stimulation scores did not differ between year 1 and 10, this 20% deterioration of on-DBS scores was interpreted as a habituation. There was no significant increase in stimulation parameters beyond the first year.

Conclusions: This 10 year follow up study, found cZi/PSA DBS for ET to be a safe procedure with a mostly retained effect on tremor, compared to 1 year after surgery, and in the absence of increase in stimulation parameters. The modest deterioration of effect of DBS on tremor was interpreted as habituation.

Essential tremor (ET) is characterized by bilateral upper limb postural and/or kinetic tremor, but also cognitive deficits. Tremor in ET, as well as aspects of cognitive deficits associated with ET, have been suggested to be linked to dysfunction in the cerebello-thalamo-cerebral circuit. In ET patients with disabling and medically intractable motor symptoms, Deep Brain Stimulation (DBS) is effective in reducing tremor. DBS in the caudal Zona incerta (cZi) has been shown to modulate the activity of the sensorimotor cerebello-cerebral circuit during motor tasks. Whether the activity in the cerebello-cerebral circuit is modulated by DBS during tasks involving working memory is unknown. The present study therefore aimed to investigate the possible effects of cZi DBS on working-memory processing in ET patients by means of task-based blood oxygen level-dependent (BOLD) fMRI.

Thirteen ET patients completed a working-memory task during DBS OFF and ON conditions. The task involved three conditions: maintenance, manipulation, and control. Behaviorally, there was no significant effect from DBS on accuracy, but a marginally significant Task x DBS interaction was detected for response times (RTs). However, post hoc comparisons for each condition failed to reach statistical significance. FMRI analyses revealed that DBS did not alter BOLD signal in regions of interest (lateral prefrontal cortex, parietal cortex, and the cerebellum), or in a complementary whole-brain analysis.

The present study indicates that DBS in the cZi in patients with ET has at most marginal effects on working memory, which is consistent with the results of pre- and post-DBS neuropsychological assessment showing minimal cognitive effects of surgery.

The nervous system exists to generate adaptive behaviour by processing sensory input from the body and the environment in order to produce appropriate motor output, and vice versa. Consequently, sensorimotor dysfunction is the basis of disability in most neurological pathologies. In the current thesis, I explore two conditions with different types and degrees of sensorimotor dysfunction by means of functional magnetic resonance imaging (fMRI). In part 1, I assess residual sensory connections to the brain in clinically complete spinal cord injury (SCI) with seemingly complete loss of sensorimotor function below the injury level. In part 2, fMRI is combined with deep brain stimulation (DBS) to investigate interventional mechanisms of restoring dysfunctional sensorimotor control in essential tremor (ET).

Part 1: SCI disrupts the communication between the brain and below-injury body parts, but rarely results in complete anatomical transection of the spinal cord. In studies I and II, we demonstrate somatosensory cortex activation due to somatosensory (tactile and nociceptive) stimulation on below-level insensate body parts in clinically complete SCI. The results from studies I and II indicate preserved somatosensory conduction across the spinal lesion in some cases of clinically complete SCI, as classified according to international standards. This subgroup is referred to as sensory discomplete SCI, which represents a distinct injury phenotype with an intermediate degree of injury severity between clinically complete and incomplete SCI.

Part 2: ET is effectively treated with DBS in the caudal zona incerta, but the neural mechanisms underlying the treatment effect are poorly understood. By exploring DBS mechanisms with fMRI, DBS was shown to cause modulation in the activity of the sensorimotor cerebello-cerebral regions during motor tasks (study III), but did not modulate the functional connectivity during resting-state (study IV).

fMRI is a valuable tool to investigate sensorimotor dysfunction and restoration in SCI and DBS-treated ET. There is evidence for sensory discomplete SCI in about half of the patients with clinically complete SCI. DBS modulates DBS modulation of the activity in the sensorimotor cerebello-cerebral circuit during motor tasks, but not during resting-state, is action-dependent.

Background: The extent of neurodegeneration underlying essential tremor (ET) remains a matter of debate. Despite various extents of cerebellar atrophy on structural magnetic resonance imaging (MRI), previous studies have shown substantial heterogeneity and included a limited number of patients. Novel automated pipelines allow detailed segmentation of cerebellar lobules based on structural MRI. Objective: To compare the volumes of cerebellar lobules in ET patients with those in healthy controls (HCs) using an automated segmentation pipeline. Methods: Structural MRI scans of ET patients eligible for deep brain stimulation (n = 55) and of age-matched and gender-matched HCs (n = 55, from the IXI database) were segmented using the automated CEREbellum Segmentation pipeline. Lobule-specific volume differences between the ET and HC groups were evaluated using a general linear model corrected for multiple tests. Results: Total brain tissue volumes did not differ between the ET and HC groups. ET patients demonstrated reduced volumes of lobules I-II, left Crus II, left VIIB, and an increased volume of right X when compared with the HC group. Conclusion: A large cohort of ET patients demonstrated subtle signs of decreased cerebellar lobule volumes. These findings oppose the hypothesis of localized atrophy in cerebellar motor areas in ET, but not the possibility of cerebellar pathophysiology in ET. Prospective investigations using alternative neuroimaging modalities may further elucidate the pathophysiology of ET and provide insights into diagnostic and therapeutic approaches.

Essential tremor is effectively treated with deep brain stimulation (DBS), but the neural mechanisms underlying the treatment effect are poorly understood. Essential tremor is driven by a dysfunctional cerebello-thalamo-cerebral circuit resulting in pathological tremor oscillations. DBS is hypothesised to interfere with these oscillations at the stimulated target level, but it is unknown whether the stimulation modulates the activity of the cerebello-thalamo-cerebral circuit during different task states (with and without tremor) in awake essential tremor patients. To address this issue, we used functional MRI in 16 essential tremor patients chronically implanted with DBS in the caudal zona incerta. During scanning, the patients performed unilateral tremor-inducing postural holding and pointing tasks as well as rest, with contralateral stimulation turned On and Off.

We show that DBS exerts both task-dependent as well as task-independent modulation of the sensorimotor cerebello-cerebral regions (p ​≤ ​0.05, FWE cluster-corrected for multiple comparisons). Task-dependent modulation (DBS ​× ​task interaction) resulted in two patterns of stimulation effects. Firstly, activity decreases (blood oxygen level-dependent signal) during tremor-inducing postural holding in the primary sensorimotor cortex and cerebellar lobule VIII, and activity increases in the supplementary motor area and cerebellar lobule V during rest (p ​≤ ​0.05, post hoc two-tailed t-test). These effects represent differences at the effector level and may reflect DBS-induced tremor reduction since the primary sensorimotor cortex, cerebellum and supplementary motor area exhibit less motor task-activity as compared to the resting condition during On stimulation. Secondly, task-independent modulation (main effect of DBS) was observed as activity increase in the lateral premotor cortex during all motor tasks, and also during rest (p ​≤ ​0.05, post hoc two-tailed t-test). This task-independent effect may mediate the therapeutic effects of DBS through the facilitation of the premotor control over the sensorimotor circuit, making it less susceptible to tremor entrainment.

Our findings support the notion that DBS in essential tremor is modulating the sensorimotor cerebello-cerebral circuit, distant to the stimulated target, and illustrate the complexity of stimulation mechanisms by demonstrating task-dependent as well as task-independent actions in cerebello-cerebral regions.

Objective: Spinal cord injury (SCI) disrupts the communication between brain and body parts innervated from below-injury spinal segments, but rarely results in complete anatomical transection of the spinal cord. The aim of this study was to investigate residual somatosensory conduction in clinically complete SCI, to corroborate the concept of sensory discomplete SCI.

Methods: We used fMRI with a somatosensory protocol in which blinded and randomized tactile and nociceptive stimulation was applied on both legs (below-injury level) and one arm (above-injury level) in eleven participants with chronic complete SCI. The experimental design accounts for possible confounding mechanical (e.g. vibration) and cortico-cortical top-down mechanisms (e.g. attention/expectation).

Results: Somatosensory stimulation on below-level insensate body regions activated the somatotopically corresponding part of the contralateral primary somatosensory cortex in six out of eleven participants.

Conclusions: Our results represent afferent-driven cortical activation through preserved somatosensory connections to the brain in a subgroup of participants with clinically complete SCI, i.e. sensory discomplete SCI.

Significance: Identifying patients with residual somatosensory connections might open the door for new rehabilitative and restorative strategies as well as inform research on SCI-related conditions such as neuropathic pain and spasticity.