Insulin: An Emerging Treatment for Alzheimer’s Disease Dementia?

Accumulating evidence indicates a role for metabolic dysfunction in the pathogenesis of Alzheimer's disease (AD). It is widely reported that Type 2 diabetes (T2D) increases the risk of developing AD, and several postmortem analyses have found evidence of insulin resistance in the AD brain. Thus, insulin-based therapies have emerged as potential strategies to slow cognitive decline in AD. The main methods for targeting insulin to date have been intravenous insulin infusion, intranasal insulin administration, and use of insulin sensitizers. These methods have elicited variable results regarding improvement in cognitive function. This review will discuss the rationale for targeting insulin signaling to improve cognitive function in AD, the results of clinical studies that have targeted insulin signaling, and what these results mean for future studies of the role of insulin-based therapies for AD.     

Spinal Cord Stimulation–Naïve Patients vs Patients With Failed Previous Experiences With Standard Spinal Cord Stimulation: Two Distinct Entities or One Population?

IntroductionNowadays, the success of spinal cord stimulation (SCS) is evaluated separately in patients who have previous experiences with standard SCS and in SCS-naïve patients. Nevertheless, it is yet to be evaluated whether both patient groups are effectively distinct patient groups. Therefore, the aims of this study are twofold: 1) Are there clusters in the data to distinguish between both patient groups? 2) Can we discriminate both patient groups based on routinely collected clinical parameters?Materials and MethodsBaseline data from the Discover study were used, in which 263 patients with persistent spinal pain syndrome type 2 were included (185 neurostimulation-naïve patients and 78 patients with previous SCS experience). Pain intensity scores for low back and leg pain, functional disability, medication use, and health-related quality of life utility scores were used in the analysis. Model-based clustering was performed on standardized data. Discriminant analysis was performed with linear and quadratic discriminant analysis, with leave-one-out cross-validation to evaluate model performance.ResultsModel-based clustering revealed two different clusters in the data. None of the clusters clearly separated SCS-naïve patients from patients with previous SCS experience. Linear discriminant analysis resulted in a leave-one-out cross-validation error rate of 30.0% to discriminate between both patient groups, based on routinely collected clinical parameters.ConclusionsClustering analysis did not result in clusters that separate SCS-naïve patients from patients with previous SCS experience. This may suggest that both patient groups should not be considered as two different patient groups when comparing them on routine clinical parameters, with potentially profound implications for research and clinical settings.Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the Discover study is NCT02787265.     

Spinal Cord MRI Hyperintensities in Cervical Spondylosis: An Ischemic Pathogenesis?

The pathophysiology of focal spinal cord MRI T2 hyperintensity (SCHI) in patients with cervical spondylosis is uncertain. This study was undertaken to determine the frequency and cause of SCHI. The authors reviewed serial cervical spine magnetic resonance imaging (MRI) reports and reviewed scans with spondylosis and cord compression or SCHI. The authors noted the location, shape, and extent of SCHI, and severity of spondylosis (expressed as a spondylosis score [SS]). The authors recorded the age and vascular risk factors for each patient. Nineteen of 273 scans (7%) with cervical spondylosis and 19 of 36 scans (53%) with cord compression had SCHI. The SCHI extended for one vertebral level from the compression in 12 patients and for three vertebral levels in 5 patients, and were distant from the compression in 2 patients. The SCHI had a focal, symmetrical, anterior spinal artery terminal zone location in 16 of 19 scans (84%). A rim isointense with normal cord separated all SCHI from the pial surface. Patients with SCHI were older (58.3 years ± 12.8 years versus 46.8 ± 8.1 years) (p = 0.007) and had a higher SS (5.7 ± 2.4 versus 3.9 ± 1.4) (p = 0.02) than patients without SCHI. The SCHI relates to the severity of cervical spondylosis. The anterior spinal artery territory location, the normal cord between SCHI and the compressive lesion, and the presence of SCHI at a distance from the compressive level all suggest an ischemic basis for SCHI.     

Spinal Cord Stimulation: A Reasonable Alternative Treatment in Patients With Symptomatic Adult Scoliosis for Whom Surgical Therapy Is Not Suitable? A Pilot Study

IntroductionIn adult scoliosis, dorsal instrumentation and fusion can provide significant improvement of pain and disability scores (Owestry Index); however, complication rates of up to 39% have been reported. As such, recent attempts have been made at expanding the surgical spectrum to include less invasive techniques in patients such as neuromodulation, specifically spinal cord stimulation (SCS). We therefore aimed to evaluate its use in a larger cohort of adult scoliosis patients in the form of a pilot study.Materials and MethodsWe analyzed prospectively collected data from 18 adult scoliosis patients receiving SCS treatment in our institution between February 2019 and May 2020. Clinical follow-up was performed at 3, 6, and 12 months following implantation of an epidural SCS System. Patients reported numeric rating scale (NRS) values for the categories of lower back pain (LBP) and regional pain (RP) both at rest and in motion. Further, SF-36, ADS-K, PSQI, and ODI forms were completed. The study was approved by the institutional Ethics Committee (EA2/093/13).ResultsInitial preoperative NRS of LBP at rest was significantly reduced following SCS at three (45% reduction, p = 0.005) and six (43% reduction, p = 0.009) months follow-up. LBP in motion was also reduced at three (27% reduction, p = 0.002) and six (33% reduction vs. preoperative, p = 0.005) months. RP at rest was reduced at three (38% reduction, p = 0.003) and six (37% reduction, p = 0.007) and in movement at three (29% reduction, 0.006) and six (32% reduction, p = 0.011). Loss of thoracic kyphosis and increased pelvic incidence were associated with worse NRS response to SCS stimulation at six months follow-up.DiscussionIn overweight, older adults for whom the risks of corrective surgery must be carefully considered, neuromodulation can significantly reduce LBP as well as regional pain in the first six months following implantation. These findings may provide a reasonable alternative in patients not willing or eligible to undergo extensive corrective surgery.     

The Neurostimulation Appropriateness Consensus Committee (NACC): Recommendations for Surgical Technique for Spinal Cord Stimulation

IntroductionThe field of neurostimulation for the treatment of chronic pain is a rapidly developing area of medicine. Although neurostimulation therapies have advanced significantly as a result of technologic improvements, surgical planning, device placement, and postoperative care are of equal importance to optimize outcomes. This Neurostimulation Appropriateness Consensus Committee (NACC) project intends to provide evidence-based guidance for these often-overlooked areas of neurostimulation practice.Materials and MethodsAuthors were chosen based on their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from the last NACC publication in 2017 to the present. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on evidence strength and consensus when evidence was scant.ResultsThis NACC project provides guidance on preoperative assessment, intraoperative techniques, and postoperative management in the form of consensus points with supportive evidence. These results are based on grade of evidence, strength of consensus, and expert opinion.ConclusionsThe NACC has given guidance for a surgical plan that encompasses the patient journey from the planning stage through the surgical experience and postoperative care. The overall recommendations are designed to improve efficacy and the safety of patients undergoing these neuromodulation procedures and are intended to apply throughout the international community.     

Is Spinal Cord Stimulation Still Effective After One or More Surgical Revisions?

ObjectivesSpinal cord stimulation (SCS) is burdened with surgical complications that may require one or several surgical revision(s), challenging its risk/benefit ratio and cost-effectiveness. Our objective was to evaluate its outcome and efficacy after one or more SCS surgical revisions.Materials and MethodsWe identified and retrospectively analyzed 116 patients treated by tonic paresthesia-based SCS who experienced one or more complication(s) requiring at least one surgical revision. Data collected included initial indication, revision indication, number of revisions, and lead design (paddle or percutaneous). Outcome after SCS revision was evaluated by pain intensity decrease (comparing baseline and postrevision Numerical Rating Scale [NRS] scores) and percentage of patients reporting pain relief ≥50%. Outcome was analyzed according to the number of surgical revisions and the revision indications.ResultsMost of the patients (61%) underwent only one revision (mean delay after implantation 44 months). The most frequent causes of revisions were hardware dysfunction (32%), lead migration (23%), and infection (18%). Revision(s) repaired the SCS issue in 87% of the cases. One year after the first revision, 82% of the patients reported pain relief ≥50%, and the mean NRS decrease was 4.0 compared with baseline (p < 0.001). Benefit of SCS revision tended to decrease with the number of revisions but did not differ across revision indications. No serious surgical complications related to the revision occurred, except for three hematomas occurring after repeated revisions.ConclusionsOur data suggest that surgical revision of SCS system is safe and led to significant pain relief in most of the cases, provided that the initial indication was good and that the previous stimulation was effective. However, success of SCS revision decreases with the number of revisions.     

Preoperative Thoracic Spine Magnetic Resonance Imaging for Spinal Cord Stimulation: Should Such a Recommendation Be an Absolute Requirement?

ObjectiveCurrent published guidelines recommend advanced imaging, specifically, thoracic magnetic resonance imaging (MRI), prior to implantation of epidural paddle spinal cord stimulator (SCS) leads. Preoperative imaging may affect surgical approach to minimize risk of complications. We aimed to assess the impact of preoperative thoracic MRI on surgical planning in a large series of surgical paddle SCS lead placements in a real-world setting.Materials and MethodsThis is a retrospective study of a prospectively maintained data base of 160 patients treated by SCS with awake thoracic surgical paddle lead placement in a single academic functional neurosurgery center from 2013 to 2021. All patients had a thoracic MRI prior to implantation. Abnormal MRI findings were reviewed to determine their potential impact on the safety of surgical paddle lead placement. A minor impact was defined as anatomical areas to avoid with paddle lead placement. Major impacts included significant deviations from standard approach to electrode placement.ResultsNone of the 160 patients had signs or symptoms referable to thoracic spine pathology prior to lead implant. Sixty-seven had abnormal thoracic MRI findings, and 36 had abnormal MRI findings that impacted surgical planning. Thirty-one patients had MRI findings with minor impact. Five patients (more than 3%) had findings with major impact.ConclusionsThis is the largest case series assessing the impact of preoperative thoracic MRI on surgical planning for patients undergoing paddle SCS placement. Twenty-two percent of patients had MRI findings that impacted surgical planning with 3% requiring additional surgical decompression for safe paddle lead placement. Without advanced imaging to inform surgical planning, unnecessary risk may have been placed on these patients. Although such imaging has been recommended by consensus committees in published guidelines, our study is the first to present a large institutional experience of real-world data that demonstrates its importance.