Safety and Efficacy of Surgical Implantation of Intrathecal Drug Delivery Pumps in Patients With Cancer With Refractory Pain.

BACKGROUND AND OBJECTIVES: Pain management in patients with cancer is a critical issue in oncology palliative care as clinicians aim to enhance quality of life and mitigate suffering. Most patients with cancer experience cancer-related pain, and 30%-40% of patients experience intractable pain despite maximal medical therapy. Intrathecal pain pumps (ITPs) have emerged as an option for achieving pain control in patients with cancer. Owing to the potential benefits of ITPs, we sought to study the long-term outcomes of this form of pain management at a cancer center. METHODS: We retrospectively reviewed medical records of all adult patients with cancer who underwent ITP placement at a tertiary comprehensive cancer center between 2013 and 2021. Baseline characteristics, preoperative and postoperative pain control, and postoperative complication rate data were collected. RESULTS: A total of 193 patients were included. We found that the average Numerical Rating Scale (NRS) score decreased significantly by 4.08 points (SD = 2.13, P < .01), from an average NRS of 7.38 (SD = 1.64) to an average NRS of 3.27 (SD = 1.66). Of 185 patients with preoperative and follow-up NRS pain scores, all but 9 experienced a decrease in NRS (95.1%). The median overall survival from time of pump placement was 3.62 months (95% CI: 2.73-4.54). A total of 42 adverse events in 33 patients were reported during the study period. The 1-year cumulative incidence of any complication was 15.6% (95% CI: 10.9%-21.1%) and for severe complication was 5.7% (95% CI: 3.0%-9.7%). Eleven patients required reoperation during the study period, with a 1-year cumulative incidence of 4.2% (95% CI: 2.0%-7.7%). CONCLUSION: Our study demonstrates that ITP implantation for the treatment of cancer-related pain is a safe and effective method of pain palliation with a low complication rate. Future prospective studies are required to determine the optimal timing of ITP implantation.

Exceptional Cases of Spinal Cord Stimulation for the Treatment of Refractory Cancer-Related Pain.

OBJECTIVES: Cancer pain has traditionally been managed with opioids, adjuvant medications, and interventions including injections, neural blockade, and intrathecal pump (ITP). Spinal cord stimulation (SCS), although increasingly used for conditions such as failed back surgery syndrome and complex regional pain syndrome, is not currently recommended for cancer pain. However, patients with cancer-related pain have demonstrated benefit with SCS. We sought to better characterize these patients and the benefit of SCS in exceptional cases of refractory pain secondary to progression of disease or evolving treatment-related complications. MATERIALS AND METHODS: This was a single-center, retrospective case series at a tertiary cancer center. Adults ≥18 years old with active cancer and evolving pain secondary to disease progression or treatment, whose symptoms were refractory to systemic opioids, and who underwent SCS trial followed by percutaneous implantation between 2016 and 2021 were included. Descriptive statistics included mean, SD, median, and interquartile range (IQR). RESULTS: Eight patients met the inclusion criteria. The average age at SCS trial was 60.0 (SD: ±11.6) years, and 50% were men. Compared with baseline, the median (IQR) change in pain score by numeric rating scale (NRS) after trial was -3 (2). At an average of 14 days after implant, the median (IQR) change in NRS and daily oral morphine equivalents were -2 (3.5) and -126 mg (1095 mg), respectively. At a median of 63 days after implant, the corresponding values were -3 (0.75) and -96 mg (711 mg). There was no significant change in adjuvant therapies after SCS implantation at follow-up. Six patients were discharged within two days after implantation. Two patients were readmitted for pain control within the follow-up period. CONCLUSIONS: In patients with cancer-related pain, SCS may significantly relieve pain, reduce systemic daily opioid consumption, and potentially decrease hospital length of stay and readmission for pain control. It may be appropriate to consider an SCS trial before ITP in select cases of cancer-related pain.

Preliminary effects of low-intensity focused ultrasound treatment program for cancer-related neuropathic pain.

Aim: To evaluate the effectiveness of low-intensity focused ultrasound (LIFU) therapy in the management of cancer-related neuropathic pain (CNP). Methods: A retrospective review with 22 patients with CNP treated with LIFU therapy (frequency 3 Hz, 3 W/cm2, pulse mode duty cycle 50%) was conducted. Results: Out of the 22 patients, 15 had CNP secondary to chemotherapy-induced peripheral neuropathy. Compared with baseline, there was a significant reduction in numeric pain rating scale (p < 0.001). Additionally, 76.5% of patients (n = 13) were considered to be responders to LIFU therapy. Conclusion: LIFU therapy may be a viable treatment modality in the management of CNP, specifically chemotherapy-induced peripheral neuropathy, with a minimal side effect profile. Larger, prospective studies with a structured protocol are necessary.

Lay abstract With recent advancements in oncological treatments, there has been an increase in the number of cancer survivors. This has led to an increase in prevalence and burden of long-term side effects of oncological disease and associated treatments. Cancer-related neuropathic pain (CNP) is a debilitating pain condition that develops in the setting of direct tumor burden or as a result of cancer-related treatments, such as chemotherapy. Management can be challenging and clinicians are often limited to pharmacological agents and more invasive modalities. This study evaluated the effectiveness of low-intensity focused ultrasound (LIFU), a noninvasive, externally applied therapeutic ultrasound device, as a treatment for CNP. Twenty-two patients with CNP were treated with LIFU and found to have significant reduction in pain, suggesting LIFU may be an effective treatment modality in the management of CNP. This pilot study has laid the ground work for future prospective studies to further investigate the effects of LIFU on CNP.

Flavonoids in the Treatment of Neuropathic Pain.

PURPOSE OF REVIEW: Chronic pain continues to present a large burden to the US healthcare system. Neuropathic pain, a common class of chronic pain, remains particularly difficult to treat despite extensive research efforts. Current pharmacologic regimens exert limited efficacy and wide, potentially dangerous side effect profiles. This review provides a comprehensive, preclinical evaluation of the literature regarding the role of flavonoids in the treatment of neuropathic pain. RECENT FINDINGS: Flavonoids are naturally occurring compounds, found in plants and various dietary sources, which may have potential benefit in neuropathic pain. Numerous animal-model studies have demonstrated this benefit, including reversal of hyperalgesia and allodynia. Flavonoids have also exhibited an anti-inflammatory effect relevant to neuropathic pain, as evidenced by the reduction in multiple pro-inflammatory mediators, such as TNF-α, NF-κB, IL-1ß, and IL-6. Flavonoids represent a potentially new treatment modality for neuropathic pain in preclinical models, though human clinical evidence is yet to be explored at this time.

Advanced Progression of Scoliosis After Intrathecal Baclofen in an Adult With Stiff Person Syndrome: A Case Report.

Stiff person syndrome is a neuroimmunological disorder characterized by progressive muscular rigidity and spasms that affect axial/limb muscles, resulting in severe pain and functional limitations. When refractory to conservative treatments, intrathecal baclofen is a viable option to treat the increased tone. Intrathecal baclofen has been shown to accelerate underlying neuromuscular scoliosis in the pediatric population with cerebral palsy. This adverse effect has never been reported in adults with stiff person syndrome. We report a case of an adult with stiff person syndrome and underlying scoliosis who experienced accelerated progression of scoliosis after initiation of intrathecal baclofen, subsequently requiring neurosurgical intervention.

Inferior and Intra-/Peri-Articular Superior Sacroiliac Joint Injection Approaches Under Ultrasound Guidance to Treat Metastasis-Related Posterior Pelvic Bone Pain.

BACKGROUND: Numerous mechanical and pathologic variables contribute to sacroiliac joint (SIJ) pain. The oncologic population has additional considerations, including tumor burden causing fracture, nerve compression, joint instability, and periosteal inflammation. Post-treatment changes may also restrict joint mobility, causing transitional pain. Currently, fluoroscopically guided SIJ injections, aimed at the inferior one third of the SIJ, are the gold standard for treatment but have only been described in the nononcologic population. Ultrasound (US) guidance may confer several benefits, including positioning, ease of procedure, lower costs, and, importantly, guidance to avoid neovascularization, metastatic disease, and other soft tissue structures. OBJECTIVES: We aim to describe the advantages of US-guided SIJ injections for refractory malignant SIJ pain from extra-articular tumors. We then describe our technique and decision framework for accessing the superior or inferior SIJ in patients with metastatic sacroiliac pain. METHODS: A retrospective review was performed on 5 patients with refractory malignant SIJ pain who underwent US-guided superior or inferior approach SIJ injection. Using imaging and outcomes, we developed a decision framework. RESULTS: Patients received either inferior or superior approach SIJ injections depending on location of tumor, extent of tumor invasion, and stability of the SIJ as per our framework. All patients reported improvement in pain and function without complications. CONCLUSIONS: We propose a decision framework for inferior vs. superior approach US-guided SIJ injections in the oncologic population with SIJ pain from metastases to the pelvis or sacrum. Having multiple techniques to approach the SIJ is important in the oncologic population, in whom metastatic tumor burden poses a technical challenge to performing these injections.

Interventional Pain Treatments in the Management of Oncologic Patients With Thoracic Spinal Tumor-Related Pain: A Case Series.

BACKGROUND: Advanced tumors of the thoracic spine are difficult to treat and can lead to complex pain syndromes. Following conventional oncologic treatments, pharmacologic therapy may be insufficient to manage pain. Minimally invasive interventional procedures offer alternatives to treat malignant thoracic spinal pain. METHODS: Thirteen patients with metastatic disease and poorly controlled thoracic axial and/or radicular pain were identified via a retrospective chart review. Patients were either treated with radiation, surgery, chemotherapy, or a combination of these. Then, the patients were organized into groups based on their diagnoses, anatomical disease locations, symptoms, prior treatments, and interventional pain procedures offered. RESULTS: All cases of intercostal nerve, costotransverse junction, erector spinae plane, and paravertebral blocks resulted in pain relief without any reported complications. A patient who received a thoracic epidural injection had a complete resolution of pain when combined with radiation therapy 2 weeks after the injection. One patient who underwent repeat thoracic epidural injections eventually had an intrathecal pump placement, resulting in reduced opioid usage. Finally, 1 patient who received a thoracic medial branch block with a relief of thoracic axial pain reported greater pain relief with a medial branch nerve cryoablation. CONCLUSION: We propose a treatment algorithm to manage patients with thoracic spinal tumor-related pain. Interventional thoracic axial procedures may be safe and efficacious pain treatments for patients with cancer.

Post-stroke rehabilitation: Factors predicting discharge to acute versus subacute rehabilitation facilities.

The aim of this study was to examine predictors of discharge of hospitalized stroke patients to either an acute inpatient rehabilitation facility (IRF) or subacute skilled nursing facility (SNF).A retrospective cohort study was done in a large multicampus urban academic medical center of individuals hospitalized for stroke between January 1, 2015 and December 31, 2015 and who were discharged to either an IRF (n = 84) or SNF (n = 59). A set of characteristics and scales were collected on each patient and assessed using univariate and multivariate regression analyses.Although univariate analyses revealed multiple measures were associated with discharge destination, the most predictive multivariate logistic regression model for discharge to SNF incorporated age (odds ratio [OR] = 1.09, 95% confidence interval [CI], 1.05-1.13), premorbid physical disability (OR 7.52, 95% CI 1.66-34.14), and inability to ambulate before discharge (OR 5.84, 95% CI 2.01-16.92) with an overall c-statistic of 0.85.Increasing age, premorbid physical disability, and inability to ambulate increase the overall likelihood of discharge to a SNF. These findings need to be replicated in larger samples to determine whether they are generalizable.

Localized Corticosteroid Injections for Malignant Joint Pain in the Oncologic Population: A Case Series.

Pain is a common issue that is present in cancer survivors as well as those with active malignant processes. Despite opioid analgesics and adjuvant therapies such as systemic corticosteroids, many patients have persistent localized pain. We describe a case series of 3 cancer patients who have concurrent hip- and greater trochanteric-related pain. We performed a single-insertion-site, ultrasound-guided injection to target both the intra-articular hip and greater trochanteric bursa for each patient. All patients reported an improvement in pain symptoms and function with no major complications. Targeted corticosteroid injections provide a potential for relief of malignant joint pain.

Spatiotemporal mapping of brain atrophy in mouse models of Huntington's disease using longitudinal in vivo magnetic resonance imaging.

Mouse models of Huntington's disease (HD) that recapitulate some of the phenotypic features of human HD, play a crucial role in investigating disease mechanisms and testing potential therapeutic approaches. Longitudinal studies of these models can yield valuable insights into the temporal course of disease progression and the effect of drug treatments on the progressive phenotypes. Atrophy of the brain, particularly the striatum, is a characteristic phenotype of human HD, is known to begin long before the onset of motor symptoms, and correlates strongly with clinical features. Elucidating the spatial and temporal patterns of atrophy in HD mouse models is important to characterize the phenotypes of these models, as well as evaluate the effects of neuroprotective treatments at specific time frames during disease progression. In this study, three dimensional in vivo magnetic resonance imaging (MRI) and automated longitudinal deformation-based morphological analysis was used to elucidate the spatial and temporal patterns of brain atrophy in the R6/2 and N171-82Q mouse models of HD. Using an established MRI-based brain atlas and mixed-effects modeling of deformation-based metrics, we report the rates of progression and region-specificity of brain atrophy in the two models. Further, the longitudinal analysis approach was used to evaluate the effects of sertraline and coenzyme Q(10) (CoQ(10)) treatments on progressive atrophy in the N171-82Q model. Sertraline treatment resulted in significant slowing of atrophy, especially in the striatum and frontal cortex regions, while no significant effects of CoQ(10) treatment were observed. Progressive cortical and striatal atrophy in the N171-82Q mice showed significant positive correlations with measured functional deficits. The findings of this report can be used for future testing and comparison of potential therapeutics in mouse models of HD.

Local presynaptic activity gates homeostatic changes in presynaptic function driven by dendritic BDNF synthesis.

Homeostatic synaptic plasticity is important for maintaining stability of neuronal function, but heterogeneous expression mechanisms suggest that distinct facets of neuronal activity may shape the manner in which compensatory synaptic changes are implemented. Here, we demonstrate that local presynaptic activity gates a retrograde form of homeostatic plasticity induced by blockade of AMPA receptors (AMPARs) in cultured hippocampal neurons. We show that AMPAR blockade produces rapid (<3 hr) protein synthesis-dependent increases in both presynaptic and postsynaptic function and that the induction of presynaptic, but not postsynaptic, changes requires coincident local activity in presynaptic terminals. This "state-dependent" modulation of presynaptic function requires postsynaptic release of brain-derived neurotrophic factor (BDNF) as a retrograde messenger, which is locally synthesized in dendrites in response to AMPAR blockade. Taken together, our results reveal a local crosstalk between active presynaptic terminals and postsynaptic signaling that dictates the manner by which homeostatic plasticity is implemented at synapses.