Loss of effectiveness with an implanted drug delivery system for intrathecal pain therapy due to corrosion.

INTRODUCTION: Intrathecal drug delivery is an established invasive treatment option. Most common complication is catheter malfunction, which can lead to overdose or withdrawal. CASE PRESENTATION: A 61-year-old female patient underwent an elective replacement of an intrathecal drug delivery pump. The patient complained about a loss of effectiveness over the past 2 years. Intraoperatively, a white mass corresponding to morphine precipitation in the pump pocket was found, which appeared to be due to corrosion at the pump-catheter connection site. CONCLUSIONS: Recommendations on how to deal with the decreasing effectiveness of intrathecal drug delivery and on intraoperative catheter handling are provided.

Spinal Neuromodulation for Peripheral Arterial Disease of Lower Extremities: A Ten-Year Retrospective Analysis.

OBJECTIVE: This long-term retrospective study evaluated the survival and amputation outcome of subjects who received neuromodulation therapy for the management of peripheral arterial disease (PAD). MATERIALS AND METHODS: The study reviews the health data of a single cohort of 51 patients who received spinal neuromodulation (spinal cord stimulation [SCS] or dorsal root ganglion stimulation [DRG-S]) for PAD from 2007 to 2022 in a single German center. Survival rate and major amputation rate were determined. Pain, quality of life, walking distance, and opioid usage were assessed before implantation (baseline), one, six, and 12 months (M) after implantation, and then annually (during a follow-up visit). Implant-related complications also were documented. RESULTS: In total, 51 patients (37 men [mean age 68.9 ± 10.2 years], 14 women [mean age (68.7 ± 14.6 years]) underwent SCS (n = 49) or DRG-S (n = 2) implantation owing to persistent ischemic pain. The follow-up mean years ± SD is 4.04 ± 2.73. At baseline, patients were classified as Rutherford's category 3 (n = 23), category 4 (n = 15) or category 5 (n = 9). At 24 M, 42 of 47 patients did not require a major amputation after the implant. All the patients reported nearly complete pain relief from pain at rest. A total of 75% of patients were able to walk >200 m, and 87% of patients who used opioids at baseline were off this medication at 24 M. Overall, 93% of patients reported an improvement in their overall health assessment. These improved outcomes were sustained through years three to 10 for patients who have reported outcomes. CONCLUSIONS: Our single-center data support the efficacy of spinal neuromodulation for improvements in limb salvage, pain relief, mobility, and quality of life. The data also show that neuromodulative therapy has a long-term therapeutic effect in patients with chronic limb pain with Rutherford category 3, 4, and 5 PAD.

[Spinal anesthesia for patients harboring a neurostimulator]. / Spinalanästhesie bei vorhandenem Neurostimulator.

This article presents the case of an 82-year-old male patient with an implanted spinal cord stimulation system, who presented to our premedication consultation for a planned knee joint replacement. Spinal anesthesia was preferred because of the previous illnesses. In accordance with the recommendation of the treating pain physician for the puncture site, an uncomplicated L4/5 puncture was performed, and the surgery was performed with the patient under adequate spinal anesthesia. The system was checked postoperatively with regular findings.

[Need for and predictability of magnetic resonance imaging examinations in patients with implanted neurostimulators]. / Bedarf und Vorhersagbarkeit von Magnetresonanztomographieuntersuchungen bei Patienten mit implantiertem Neurostimulator.

BACKGROUND: With an increasing number of magnetic resonance imaging (MRI) examinations in the general population, there are no data available regarding the requirements of patients with implanted neurostimulators in Germany. Published data from the United States of America suggest a high need. The limited approval for MRI scans of implants are a common problem. OBJECTIVE: The focus is on the MRI needs of these pain patients and the predictability at the time of implantation. MATERIAL AND METHOD: We carried out a retrospective evaluation of the database of our hospital information system. We searched for all MRI requests for patients with an implanted neurostimulator between November 2011 and March 2019. In addition, we compared these data with the implantation of neurostimulators in the same period. RESULTS: We identified 171 MRI examinations and 22 requests without a subsequent examination. Out of 294 (28%) patients implanted in our center 83 had at least 1 MRI scan in our hospital. We observed a steadily increasing demand. In 111 of 171 (65%) performed examinations, there was no association between the indications leading to neurostimulator implantation and to MRI. A predictability could only be assumed for 43 of 193 (22%) MRI requests. CONCLUSION: In Germany, patients with an implanted neurostimulator have a high need for MRI diagnostics which cannot be predicted at the time of implantation. Therefore, only MRI-conditional systems should be implanted. The manufacturers need to adapt the implants and their approval to requirements.

Dorsal root ganglion stimulation for treatment of central poststroke pain in the lower extremity after medullary infarction.

ABSTRACT: We report a case of relief in central poststroke pain of the lower extremity by stimulation of the dorsal root ganglion (DRG). Central poststroke pain is a poorly understood and even more poorly managed condition that can greatly impact the quality of life. To the best of our knowledge, this investigation is the first to describe the successful treatment of previously intractable chronic pain caused by stroke using DRG stimulation. Noting the anatomical structures and the physiological function, the efficacy of DRG stimulation in central poststroke pain could be explained in a neurophysiological manner. This clinical observation successfully builds on the existing understanding around the pathophysiology of central pain and offers the possibility of nondrug therapy for the treatment of this often refractory chronic pain syndrome.

Magnetic resonance imaging scans in patients with dorsal root ganglion stimulation.

OBJECTIVE: Patients fitted with a neurostimulator face a greater need to undergo magnetic resonance imaging (MRI) scans. Given the lack of literature in this regard, this study aims to review our experience with MRI examinations on patients implanted with a dorsal root ganglion stimulation (DRG-S) system and their potential adverse events. MATERIALS AND METHODS: We conducted a retrospective analysis of the prospective treatment documentation gathered from November 2011 to October 2020. We identified 259 MRI registrations for patients with an implanted neurostimulation system; the MRI examinations were performed using a 1.5 Tesla MRI system in accordance with a structured scheme. RESULTS: Among the 259 MRI registrations identified in this study, 28 corresponded to patients with an implanted DRG-S system. In 2 cases, no MRI scan was performed, and thus, only 26 MRI examinations were evaluated in detail. The DRG-S device was approved for the requested MRI scans in only 2 of these 26 cases (7.7%). In addition, 2 minor adverse events (syncopal episode and connection problem) were identified, and only the second problem (3.8%) was related to neurostimulator operation. CONCLUSIONS: Necessary MRI examinations in patients with DRG-S systems are rarely covered by the European CE/US Food and Drug Administration (CE/FDA) approval. Although the manufacturer recommendations are against the use of MRI in patients with implanted DRG-S in certain conditions, we performed these scans without causing injury to the patient or damaging the device. Given that data on safety are limited, MRIs should be conducted study related. We provide recommendations for the procedure that should be followed when an MRI is needed urgently.

Three-Year Outcomes After Dorsal Root Ganglion Stimulation in the Treatment of Neuropathic Pain After Peripheral Nerve Injury of Upper and Lower Extremities.

OBJECTIVES: Traumatic peripheral nerve injuries (PNI) often result in severe neuropathic pain which typically becomes chronic, is recalcitrant to common analgesics, and is associated with sleep disturbances, anxiety, and depression. Pharmacological treatments proven to be effective against neuropathic pain are not well tolerated due to side effects. Neuromodulative interventions such as peripheral nerve or spinal cord stimulation have generated mixed results and may be limited by reduced somatotopic specificity. Dorsal root ganglion (DRG) stimulation may be more effective in this etiology. MATERIALS AND METHODS: Twenty-seven patients were trialed with a DRG neurostimulation system for PNI; trial success (defined as ≥50% pain relief) was 85%, and 23 patients received a permanent stimulator. However, 36-month outcome data was only available for 21 patients. Pain, quality of life, mental and physical function, and opioid usage were assessed at baseline and at 3-, 6-, 12-, 18-, 24-, and 36 months post-permanent implant. Implant-related complications were also documented. RESULTS: Compared to baseline, we observed a significant pain relief (p < 0.001) at 3 (58%), 12 (66%), 18 (69%), 24 (71%), and 36 months (73%) in 21 patients (52.5 ± 14.2 years; 12 female), respectively. Mental and physical function showed immediate and sustained improvements. Participants reported improvements in quality of life. Opioid dosage reduced significantly (p < 0.001) at 3 (30%), 12 (93%), 18 (98%), 24 (99%), and 36 months (99%), and 20 of 21 patients were completely opioid-free after 36 months. There were five lead migrations and two electrode fractures (corrected by surgical intervention) and one wound infection (conservatively managed). CONCLUSIONS: DRG neuromodulation appears to be a safe, effective, and durable option for treating neuropathic pain caused by PNI. The treatment allows cessation of often ineffective pharmacotherapy (including opioid misuse) and significantly improves quality of life.

Role of neutral amino acid transport and protein breakdown for substrate supply of nitric oxide synthase in human endothelial cells.

Endothelial dysfunction is often associated with a relative substrate deficiency of the endothelial nitric oxide synthase (eNOS) in spite of apparently high intracellular arginine concentrations. For a better understanding of the underlying pathophysiological mechanisms, we aimed to characterize the intracellular arginine sources of eNOS. Our previous studies in human endothelial EA.hy926 cells suggested the existence of two arginine pools: pool I can be depleted by extracellular lysine, whereas pool II is not freely exchangeable with the extracellular space, but accessible to eNOS. In this study, we demonstrate that the eNOS accessible pool II is also present in human umbilical vein endothelial cells (HUVECs), but not in ECV bladder carcinoma cells transfected with an expression plasmid for eNOS. In the endothelial cells, one part of pool II (referred to as pool IIA) consisted of recycling of citrulline to arginine. This part could be depleted by neutral amino acids that match the substrate profile of system N transporter 1 (SN1), presumably by the removal of intracellular citrulline. SN1 was expressed in EA.hy926 cells and HUVECs as shown by real-time RT-PCR. The second part of pool II (referred to as pool IIB) could not be depleted by any of the cationic or neutral amino acids tested. Our data demonstrate that pool IIB is nourished by protein breakdown and thus represents a substrate pool likely to accumulate protein-derived endogenous inhibitors of eNOS. Preferential use of the arginine pool IIB under pathophysiological conditions might therefore explain the arginine paradox.