Low-frequency dorsal root stimulation is effective for various pain etiologies and pain locations.

BACKGROUND: Dorsal root ganglion stimulation (DRG-S) has emerged as a novel therapeutic approach for managing chronic neuropathic pain. AIMS: This study aims to compare the effectiveness of 4-20 Hz DRG-S through a retrospective analysis of a cohort of 28 patients with various neuropathic pain etiologies and pain locations. MATERIALS AND METHODS: Patient responses to both stimulation frequencies were examined using the Numeric Rating Scale (NRS) and Patient Global Impression of Change (PGIC) assessments. Factors such as patient preference and satisfaction were also evaluated. RESULTS: The results indicate that 4 Hz DRG-S is not only as effective as 20 Hz stimulation but may also surpass it. Among the 28 patients, 26 assessed 4 Hz stimulation to be at least as effective as 20 Hz, with the majority (22 out of 26) considering 4 Hz stimulation superior. After trying 4 Hz stimulation, 24 out of 28 patients chose it over 20 Hz, while two patients opted for a combination of both settings. Only two patients reverted to their original 20 Hz stimulation program. A statistically significant pain reduction of 24% was observed when comparing the effects of 4 Hz versus 20 Hz. DISCUSSION: The study highlights the broader applicability of low-frequency DRG-S, extending its benefits beyond the realm of low back pain. Patients with diverse pain etiologies and locations experienced comparable positive outcomes, suggesting that the advantages of low-frequency stimulation are not confined to specific pain types or locations. CONCLUSION: This study emphasizes the potential of 4 Hz DRG-S as a valuable alternative to the standard 20 Hz stimulation. Although the exact mechanisms require further investigation, the observed clinical benefits and patient preferences for low-frequency stimulation suggest its viability across diverse pain indications and locations. Additional research is necessary to substantiate these findings and assess the durability and economic implications of low-frequency DRG-S.

Bilateral T12 Dorsal Root Ganglion Stimulation for the Treatment of Low Back Pain With 20-Hz and 4-Hz Stimulation, a Retrospective Study.

OBJECTIVES: Chronic low back pain (CLBP) is one of the most common chronic pain conditions that cause both individual suffering and a burden to society. For these patients, several interventional treatment options such as surgery, blocks, radiofrequency, and spinal cord stimulation are available. Lately, dorsal root ganglion stimulation (DRG-S) also has been mentioned as an option by targeting bilateral T12 dorsal ganglia. In this study, we present the outcome of 11 patients with CLBP treated with bilateral T12 DRG-S. MATERIALS AND METHODS: Thirteen patients with CLBP with and without leg pain were treated with bilateral T12 DRG-S. Three of the patients also received a third lumbar lead owing to leg pain. Eleven of the patients had >50% pain relief during the peri- or/and postoperative testing and received a fully implantable neurostimulator. Pain intensity, general health status, quality of life, pain catastrophizing, mental status, sleeping disorder, physical activity, and patient satisfaction were followed using numeric rating scale (NRS), Patient-Reported Outcomes Measurement Information System 29 version 2.1, Pain Catastrophizing Score, Generalized Anxiety Disorder 7-item scale, Patient Health Questionnaire Depression Module, Insomnia Severity Index, and Patient Satisfaction Questionnaire at baseline before implantation and at three months and six months. The results were analyzed on the basis of six domains: pain relief, sleeping disorder, social ability, mental status, physical activity, and satisfaction. To be identified as a responder, the patients should show a significant improvement in the pain relief domain together with at least two other domains. All responders also were given the opportunity to test 4-Hz DRG-S and compare it with traditional 20-Hz stimulation. RESULTS: All 11 patients were identified as responders at six months. Five of the patients had >80% pain relief, with an average NRS score reduction of 71% for the whole group. Significant improvement could be observed in three domains for one patient, four domains for three patients, five domains for six patients, and six domains for one patient. Seven patients chose to try 4-Hz stimulation. All seven identified 4-Hz stimulation as at least as good as or better than 20-Hz stimulation and chose to continue with 4-Hz stimulation. CONCLUSIONS: Bilateral T12 DRG-S seems to be an effective treatment for chronic low back pain, with significant beneficial effect not only on pain but also on quality of life, pain catastrophizing, mental status, sleeping disorder, and physical activity. 4-Hz DRG-S gave a result comparable with or better than 20-Hz stimulation.

Vertigo: Could this Symptom Indicate the Existence of an Unruptured Intracranial Aneurysm?

Background:Unruptured intracranial aneurysms (UIAs) can be presented with various symptoms, including atypical headaches and cranial nerve deficits. Vertigo is often referred in the literature as a coexisting symptom. Our aim was to investigate the importance of vertigo in the UIA symptomatology and present a possible explanation for its existence. Methods:We conducted a retrospective observational multicenter study concerning patients with surgically treated intracranial aneurysms. During a period of 10 years, 1 085 patients with cerebral aneurysms underwent surgery. There were 812 patients with ruptured intracranial aneurysms (RIA) and 273 with UIA. The medical records for each of the 273 patients were analyzed. Results: After the implementation of exclusion criteria, 89 (32.6%) of UIA patients were selected in the study, from which 71 (79.8%) were females and 18 (20.2%) males. The mean age was 56.9 (± 12.876) years old. Vertigo existed in 72 (80.9%), headache in 41 (46.1%) and visual symptoms in 21 (23.6%) patients. No significant correlation (p >0.05) was demonstrated between gender, age or aneurysm location in correlation with vertigo, headache or visual symptoms, apart from a negative significant correlation between age and vertigo (p=0.031). Conclusion:Vertigo is an alarming symptom that could indicate the existence of an UIA. The pathophysiological mechanism could be explained by the formation of an aneurysmal vortex that projects into the parent artery, leading to disturbances in the laminar flow and formation of an irregular/turbulent flow, which potentially affects the cerebral autoregulation and by consequence, the central processing of movement.

Intratumoral retrograde microdialysis treatment of high-grade glioma with cisplatin.

PURPOSE: This study evaluates the application of a microdialysis technique for interstitial chemotherapy using cisplatin in high-grade glioma. METHOD: An in vitro study demonstrated that cisplatin can be administered through retrograde microdialysis and defined the recovery for cisplatin. In a subsequent phase I study, 1-4 microdialysis catheters were implanted in tumor tissue, brain adjacent to tumor (BAT) tissue, and subcutaneous tissue in 10 patients with recurrent high-grade glioma. Cisplatin was administered continuously in daily doses between 0.3 and 3.9 mg for 4 to12 days. Microdialysis samples were continuously collected and analyzed for glucose metabolites, glutamate, glycerol, and cisplatin concentrations. Treatment tolerability was evaluated through clinical monitoring. Quality of life was assessed using the EORTC-QLQ-C30 questionnaire for up to 3 months after treatment. RESULTS: This in vitro study showed that cisplatin could be administrated with a recovery of 41-97%, depending on flowrate, type of catheter, and cisplatin concentration. During the treatment, patients were exposed to a total dose of 1.2-36.8 mg cisplatin. The concentration of cisplatin in BAT, serum, and subcutaneous tissue was close to detection level in all but two patients. A transient neurologic deterioration due to edema was commonly observed, but no systemic side effects were recorded. After onset of treatment, concentrations of glutamate and glycerol were significantly increased in tumor tissue but not in BAT, with a peak after 3 days, and consistent for the rest of the treatment. Five of the patients survived between 153 and 492 days after treatment. CONCLUSION: This phase I study demonstrates that retrograde microdialysis can be used to administer cisplatin interstitially into high-grade glioma tissue. A high cytotoxicity was detected in tumor tissue, but not in the surrounding brain. Retrograde microdialysis appears to be a clinically useful method for intratumoral drug administration in high-grade glioma.

Metabolic response patterns in brain microdialysis fluids and serum during interstitial cisplatin treatment of high-grade glioma.

BACKGROUND: High-grade gliomas are associated with poor prognosis. Tumour heterogeneity and invasiveness create challenges for effective treatment and use of systemically administrated drugs. Furthermore, lack of functional predictive response-assays based on drug efficacy complicates evaluation of early treatment responses. METHODS: We used microdialysis to deliver cisplatin into the tumour and to monitor levels of metabolic compounds present in the tumour and non-malignant brain tissue adjacent to tumour, before and during treatment. In parallel, we collected serum samples and used multivariate statistics to analyse the metabolic effects. RESULTS: We found distinct metabolic patterns in the extracellular fluids from tumour compared to non-malignant brain tissue, including high concentrations of a wide range of amino acids, amino acid derivatives and reduced levels of monosaccharides and purine nucleosides. We found that locoregional cisplatin delivery had a strong metabolic effect at the tumour site, resulting in substantial release of glutamic acid, phosphate, and spermidine and a reduction of cysteine levels. In addition, patients with long-time survival displayed different treatment response patterns in both tumour and serum. Longer survival was associated with low tumour levels of lactic acid, glyceric acid, ketoses, creatinine and cysteine. Patients with longer survival displayed lower serum levels of ketohexoses, fatty acid methyl esters, glycerol-3-phosphate and alpha-tocopherol, while elevated phosphate levels were seen in both tumour and serum during treatment. CONCLUSION: We highlight distinct metabolic patterns associated with high-grade tumour metabolism, and responses to cytotoxic cisplatin treatment.

The appropriate management of persisting pain after spine surgery: a European panel study with recommendations based on the RAND/UCLA method.

PURPOSE: Management of patients with persisting pain after spine surgery (PPSS) shows significant variability, and there is limited evidence from clinical studies to support treatment choice in daily practice. This study aimed to develop patient-specific recommendations on the management of PPSS. METHODS: Using the RAND/UCLA appropriateness method (RUAM), an international panel of 6 neurosurgeons, 6 pain specialists, and 6 orthopaedic surgeons assessed the appropriateness of 4 treatment options (conservative, minimally invasive, neurostimulation, and re-operation) for 210 clinical scenarios. These scenarios were unique combinations of patient characteristics considered relevant to treatment choice. Appropriateness had to be expressed on a 9-point scale (1 = extremely inappropriate, 9 = extremely appropriate). A treatment was considered appropriate if the median score was ≥ 7 in the absence of disagreement (≥ 1/3 of ratings in each of the opposite sections 1-3 and 7-9). RESULTS: Appropriateness outcomes showed clear and specific patterns. In 48% of the scenarios, exclusively one of the 4 treatments was appropriate. Conservative treatment was usually considered appropriate for patients without clear anatomic abnormalities and for those with new pain differing from the original symptoms. Neurostimulation was considered appropriate in the case of (predominant) neuropathic leg pain in the absence of conditions that may require surgical intervention. Re-operation could be considered for patients with recurrent disc, spinal/foraminal stenosis, or spinal instability. CONCLUSIONS: Using the RUAM, an international multidisciplinary panel established criteria for appropriate treatment choice in patients with PPSS. These may be helpful to educate physicians and to improve consistency and quality of care. These slides can be retrieved under Electronic Supplementary Material.

Radiotherapy induces an immediate inflammatory reaction in malignant glioma: a clinical microdialysis study.

The knowledge of response to radiation in the immuno-microenvironment of high grade gliomas is sparse. In vitro results have indicated an inflammatory response of myeloid cells after irradiation. Therefore, microdialysis was used to verify whether this is operative in tumor tissue and brain adjacent to tumor (BAT) after clinical radiotherapy of patients with high grade glioma. Stereotactic biopsies and implantation of microdialysis catheters in tumor tissue and BAT were performed in eleven patients with high-grade glioma. The patients were given daily radiation fractions of 2-3.4 Gy. Microdialysis samples were collected before radiotherapy and during the first five days of radiation. Cytokines, glucose metabolites, glutamate and glycerol were analyzed. Immunohistochemistry was performed to detect macrophages (CD68) and monocytes (CD163) as well as IL-6, IL-8 and MCP-1. A significant increase of IL-8, MCP-1 and MIP-1a were detected in tumor tissue already after the first dose of radiation and increased further during 5 days of radiation. IL-6 did also increase but after five fractions of radiation. In BAT, the cytokine response was modest with significant increase of IL-8 after third dose of radiation. We found a positive correlation between baseline IL-8 and IL-6 microdialysis levels in tumor tissue and survival. Glucose metabolites or glycerol and glutamate did not change during radiation. In all tumors staining for macrophages was demonstrated. IL-6 was found in viable tumor cells while MCP-1 was demonstrated in macrophages or tumor matrix. Our findings suggest that radiation induces a rapid enhancement of the prevailing inflammation in high-grade glioma tissue. The microdialysis technique is feasible for this type of study and could be used to monitor metabolic changes after different interventions.

Glucose metabolites, glutamate and glycerol in malignant glioma tumours during radiotherapy.

OBJECTIVE: The metabolism of malignant glioma was studied in 13 patients. The main objective was to perform a study of the metabolic pattern of glucose, lactate, pyruvate, glutamate and glycerol in tumour tissue during base-line conditions and to detect any changes in the metabolism during radiotherapy. METHOD: During a stereotactic biopsy, two microdialysis catheters were implanted: one in tumour and one in peri-tumoural tissue. Fasting samples were analysed daily, before and during 5 days of radiotherapy given with 2 Gy fractions. RESULTS: Base-line levels of glucose and pyruvate were significantly lower in tumour compared to peri-tumoural tissue (P = 0.04 and 0.023, respectively). The lactate/pyruvate ratio was significantly higher in tumour tissue (P = 0.022). In general, the levels of lactate, glutamate and glycerol were higher in tumour tissue, although not statistically significant. Further, we could not detect any significant changes during the 5 days of radiotherapy in any of the metabolites analysed. CONCLUSION: Radiotherapy up to 10 Gy given in five fractions does not influence the glucose metabolism nor does it induce any acute cytotoxic effect detected with glutamate or glycerol in malignant glioma, as assessed by microdialysis. The study confirms the glycolytic properties of glucose metabolism in malignant glioma.