Sharad Rajpal

The role of cation-dependent chloride transporters in neuropathic pain following spinal cord injury

BackgroundAltered Cl- homeostasis and GABAergic function are associated with nociceptive input hypersensitivity. This study investigated the role of two major intracellular Cl- regulatory proteins, Na+-K+-Cl- cotransporter 1 (NKCC1) and K+-Cl- cotransporter 2 (KCC2), in neuropathic pain following spinal cord injury (SCI).ResultsSprague-Dawley rats underwent a contusive SCI at T9 using the MASCIS impactor. The rats developed hyperalgesia between days 21 and 42 post-SCI. Thermal hyperalgesia (TH) was determined by a decrease in hindpaw thermal withdrawal latency time (WLT) between days 21 and 42 post-SCI. Rats with TH were then treated with either vehicle (saline containing 0.25% NaOH) or NKCC1 inhibitor bumetanide (BU, 30 mg/kg, i.p.) in vehicle. TH was then re-measured at 1 h post-injection. Administration of BU significantly increased the mean WLT in rats (p < 0.05). The group administered with the vehicle alone showed no anti-hyperalgesic effects. Moreover, an increase in NKCC1 protein expression occurred in the lesion epicenter of the spinal cord during day 2–14 post-SCI and peaked on day 14 post-SCI (p < 0.05). Concurrently, a down-regulation of KCC2 protein was detected during day 2–14 post-SCI. The rats with TH exhibited a sustained loss of KCC2 protein during post-SCI days 21–42. No significant changes of these proteins were detected in the rostral region of the spinal cord.ConclusionTaken together, expression of NKCC1 and KCC2 proteins was differentially altered following SCI. The anti-hyperalgesic effect of NKCC1 inhibition suggests that normal or elevated NKCC1 function and loss of KCC2 function play a role in the development and maintenance of SCI-induced neuropathic pain.

The accuracy of pedicle screw placement using intraoperative image guidance systems

OBJECT Several retrospective studies have demonstrated higher accuracy rates and increased safety for navigated pedicle screw placement than for free-hand techniques; however, the accuracy differences between navigation systems has not been extensively studied. In some instances, 3D fluoroscopic navigation methods have been reported to not be more accurate than 2D navigation methods for pedicle screw placement. The authors of this study endeavored to identify if 3D fluoroscopic navigation methods resulted in a higher placement accuracy of pedicle screws. METHODS A systematic analysis was conducted to examine pedicle screw insertion accuracy based on the use of 2D, 3D, and conventional fluoroscopic image guidance systems. A PubMed and MEDLINE database search was conducted to review the published literature that focused on the accuracy of pedicle screw placement using intraoperative, real-time fluoroscopic image guidance in spine fusion surgeries. The pedicle screw accuracy rates were segregated according to spinal level because each spinal region has individual anatomical and morphological variations. Descriptive statistics were used to compare the pedicle screw insertion accuracy rate differences among the navigation methods. RESULTS A total of 30 studies were included in the analysis. The data were abstracted and analyzed for the following groups: 12 data sets that used conventional fluoroscopy, 8 data sets that used 2D fluoroscopic navigation, and 20 data sets that used 3D fluoroscopic navigation. These studies included 1973 patients in whom 9310 pedicle screws were inserted. With conventional fluoroscopy, 2532 of 3719 screws were inserted accurately (68.1% accuracy); with 2D fluoroscopic navigation, 1031 of 1223 screws were inserted accurately (84.3% accuracy); and with 3D fluoroscopic navigation, 4170 of 4368 screws were inserted accurately (95.5% accuracy). The accuracy rates when 3D was compared with 2D fluoroscopic navigation were also consistently higher throughout all individual spinal levels. CONCLUSIONS Three-dimensional fluoroscopic image guidance systems demonstrated a significantly higher pedicle screw placement accuracy than conventional fluoroscopy or 2D fluoroscopic image guidance methods.

Comparison of perioperative oral multimodal analgesia versus IV PCA for spine surgery.

Study Design A preintervention and postintervention design was used to examine a total of 200 patients. Objective After successful implementation at our institution of a perioperative oral multimodal analgesia protocol in major joint arthroplasty, a modified regimen was provided to patients undergoing spine procedures. Summary of Background Data A proactive, multimodal approach is currently recommended for the management of acute postoperative pain. Inadequate postoperative analgesia can negatively influence surgical outcome and duration of rehabilitation. Routine use of intravenous patient controlled analgesia (IV PCA) after surgery can result in substantial functional interference, side effects, and lead to untoward events as a result of programming errors. Methods A preintervention and postintervention design was used to compare a historical control group of spine surgery patients who received conventional IV PCA (N=100) with a prospective group who received some form of perioperative oral multiodal analgesis (N=100). The new regimen included preoperative and postoperative scheduled extended-release oxycodone, gabapentin, and acetaminophen, intraoperative dolasetron and as-needed postoperative short-acting oral oxycodone. Patient surveys and chart audits were used to measure pain intensity, functional interference from pain, opioid consumption, analgesic-related side effects, and patient satisfaction over the first 24 hours postoperatively. Results Patients who received the new perioperative multimodal oral regimen had significantly less opioid consumption (P<0.001), lower ratings of Least Pain (P<0.01), and experienced less nausea (P<.001), drowsiness (P<0.05), interference with walking (P=0.05), and coughing and deep breathing (P<0.05) compared with the IV PCA group. Conclusions This quality improvement study shows some safety and significant advantages of a multimodal perioperative oral analgesic regimen compared with standard IV PCA after spine surgery.

Serum insulin-like growth factors and their binding proteins in patients with hepatic failure and after liver transplantation

The liver is the major source of circulating insulin-like growth factor-I and -II (IGF-I and IGF-II) and several of their binding proteins (BPs). This study examined the effects of end-stage liver disease (ESLD) and subsequent liver transplantation (LT) on serum levels of these growth factors and their BPs in four children and six adults for up to 2 years. Serum IGF-I and IGF-II were quantified by radioimmunoassay (RIA), IGFBP-3 by immunoradiometric assay (IRMA), and changes in IGFBP-1, -2, -3, and -4 were estimated by Western ligand blotting (WLB). In severe hepatic disease, serum concentrations of IGF-I (10 +/- 5 ng/mL) and IGF-II (126 +/- 32 ng/mL) were significantly (P < .01) less than in normal controls (170 +/- 37 and 590 +/- 41 ng/mL, respectively). One year following LT, the mean levels of IGF-I (344 +/- 55 ng/mL) and IGF-II (627 +/- 38 ng/mL) were within normal limits and remained so for the duration of the study. Patients exhibited considerable variation not only in the rate of achieving normal IGF-I and IGF-II concentrations, but also in the ultimate height and stability of these peptide levels. Serum IGFBP-3 in hepatic failure (580 +/- 140 ng/mL) was significantly (P < .05) lower than in controls (2,900 +/- 220 ng/mL) and increased to normal levels (3,650 +/- 360 ng/mL) 2 to 14 weeks after LT. Serum levels of IGFBP-1, -2, and -4 before and after LT were variable but usually remained within normal limits compared with control sera. The decreases observed in IGF-I, IGF-II, and IGFBP-3 in patients with hepatic failure and their subsequent restoration after LT probably result primarily from the reduced number of functional hepatocytes in ESLD and their subsequent replacement by healthy hepatic tissue. These changes may also result from hormonal alterations and nutritional deficiencies known to exist in patients with severe liver dysfunction, which are corrected by LT. We conclude that LT in patients with severe hepatic insufficiency enhances the potential for normal cell growth and replication by restoring serum IGF-I, IGF-II, and IGFBP-3 concentrations to normal concomitantly with the improvement in hormonal and nutritional status.

Complications in patients undergoing combined transforaminal lumbar interbody fusion and posterior instrumentation with deformity correction for degenerative scoliosis and spinal stenosis.

Background: Utilization of the transforaminal lumbar interbody fusion (TLIF) approach for scoliosis offers the patients deformity correction and interbody fusion without the additional morbidity associated with more invasive reconstructive techniques. Published reports on complications associated with these surgical procedures are limited. The purpose of this study was to quantify the intra- and postoperative complications associated with the TLIF surgical approach in patients undergoing surgery for spinal stenosis and degenerative scoliosis correction. Methods: This study included patients undergoing TLIF for degenerative scoliosis with neurogenic claudication and painful lumbar degenerative disc disease. The TLIF technique was performed along with posterior pedicle screw instrumentation. The average follow-up time was 30 months (range, 15–47). Results: A total of 29 patients with an average age of 65.9 years (range, 49–83) were evaluated. TLIFs were performed at 2.2 levels on average (range, 1–4) in addition to 6.0 (range, 4–9) levels of posterolateral instrumented fusion. The preoperative mean lumbar lordosis was 37.6° (range, 16°–55°) compared to 40.5° (range, 26°–59.2°) postoperatively. The preoperative mean coronal Cobb angle was 32.3° (range, 15°–55°) compared to 15.4° (range, 1°–49°) postoperatively. The mean operative time was 528 min (range, 276–906), estimated blood loss was 1091.7 mL (range, 150–2500), and hospitalization time was 8.0 days (range, 3–28). A baseline mean Visual Analog Scale (VAS) score of 7.6 (range, 4–10) decreased to 3.6 (range, 0–8) postoperatively. There were a total of 14 (49%) hardware and/or surgical technique related complications, and 8 (28%) patients required additional surgeries. Five (17%) patients developed pseudoarthrosis. The systemic complications (31%) included death (1), cardiopulmonary arrest with resuscitation (1), myocardial infarction (1), pneumonia (5), and pulmonary embolism (1). Conclusion: This study suggests that although the TLIF approach is a feasible and effective method to treat degenerative adult scoliosis, it is associated with a high rate of intra- and postoperative complications and a long recovery process.

Cannabinoid subtype-2 receptors modulate the antihyperalgesic effect of WIN 55,212-2 in rats with neuropathic spinal cord injury pain.

BACKGROUND CONTEXT There is increasing evidence for a role of the cannabinoid (CB) system in the development of neuropathic pain (NP) after spinal cord injury (SCI). The nonspecific CB₁ and CB₂ receptor agonists, WIN 55, 212-2 (WIN), have previously been shown to alleviate both mechanical and thermal hyperalgesia (TH) after peripheral nerve injury. PURPOSE The present study was designed to identify the CB receptors involved in the antihyperalgesic effect of WIN by using selective antagonists for CB₁ and CB₂ receptors. STUDY DESIGN This is an in vivo and behavioral study using a moderate T9 contusion SCI. After injury, TH of the hind paws was measured on postinjury days 21 through 42. METHODS Sprague-Dawley rats underwent a contusion SCI using the Multicenter Animal Spinal Cord Injury Study (MASCIS) weight-drop impactor, which induced a moderate T9 SCI. Only animals showing consistent plantar stepping and consistent forelimb and hind limb coordination (Basso, Beattie, and Bresnahan score=15) were tested for TH. Animals exhibiting decreased withdrawal latency time, indicating TH, on or before Day 42, were selected for pharmacological intervention. Animals not exhibiting TH did not receive pharmacological intervention and were sacrificed. Rats underwent hind paw testing before any drug administration (after injury), 45 minutes after selective CB antagonist (AM 251 or AM 630) administration (postantagonist) and again 45 minutes after WIN administration (post-WIN). There were a total of seven treatment groups: saline vehicle control; Dimethyl sulfoxide (DMSO) vehicle control; low-dose WIN (0.2 mg/kg); and high-dose WIN (2.0 mg/kg); AM 251 (3 mg/kg) and AM 630 (1 mg/kg) were given subcutaneously in a total volume of 0.5 mL. Followed by intraperitoneal injection of WIN after each antagonist, sham-operated rats repeated pharmacological intervention used with treatment Groups 5 and 6. RESULTS Thermal hyperalgesia was significantly ameliorated in a dose-dependent manner with systemically administered WIN. Cannabinoid receptor Type 1 antagonist AM 251 pretreatment did not affect the antihyperalgesic effect of WIN. By contrast, pretreatment with the CB₂ receptor antagonist AM 630 significantly attenuated the effect of WIN. CONCLUSION Taken together, these results suggest a role of the CB₂ receptor in modulating SCI-induced TH. Selective activation of the CB₂ receptor could potentially lead to analgesic effects on NP while avoiding psychotropic side effects in patients with SCI.

THE ROLE OF THE JOURNAL CLUB IN NEUROSURGICAL TRAINING

OBJECTIVE The journal club (JC) plays a traditional role in resident education. However, little has been written on its current role in neurosurgical training programs. Our goal was to determine resident perception of JCs, factors that make JCs successful, and identifying variables for improving JCs. METHODS We electronically surveyed all resident members of the Congress of Neurological Surgeons to determine the format, prevalence, content, and efficacy of neurosurgical JCs. RESULTS Eighty-five percent of the respondents stated that their residency programs have a JC. The perceived primary goal of JCs is for keeping current with the literature and the dissemination of information. Most JCs meet for 1 hour during the week on a monthly basis and review one to three articles. Residents generally present the articles, which are typically original research articles selected by either the faculty or the residents. Most residents consider JCs of good educational value with positive effects on reading habits. Resident and faculty attendance are important variables to a successful JC. Although the majority of residents have minimal background training in epidemiology, biostatistics, or research, fewer than one-third of the training programs provide any type of supplemental sessions or handouts regarding such methods. CONCLUSION JCs have a high perceived value by neurosurgical residents and should be maintained at all neurosurgical residency training programs. Key factors to a successful JC include faculty and resident attendance. Additional studies are needed to assess optimal JC formats and the possible utilization of supplemental educational tools.

Segmental spinal instrumentation in the management of scoliosis.

SPINAL INSTRUMENTATION FOR the correction of spinal deformity began with Harrington and his rod system. The use of the Harrington rods was limited, however, because of the need for long-segment instrumentation, distraction, and the potential for hood dislodgment and construct failure. Luque subsequently introduced the next generation of spinal fixation techniques via the concept of segmental instrumentation; his use of sublaminar wires allowed the construct to be fixated to the spine at every level. This arrangement allowed greater control over correction of spinal deformities and significantly lessened the incidence of hardware dislodgment. Modern instrumentation systems, including the use of pedicle screws, permit even greater control of the spine in multiple planes during deformity correction. Newer strategies have decreased the incidence of neurological injury during implant application and provide greater stability. A review of segmental fixation, including surgical techniques, is provided in this article.

The duration of symptoms and clinical outcomes in patients undergoing anterior cervical discectomy and fusion for degenerative disc disease and radiculopathy

BACKGROUND CONTEXT There have been controversial reports published in the literature on the duration of symptoms (DOS) and clinical outcome correlation in patients undergoing anterior cervical discectomy and fusion (ACDF) for painful degenerative disc disease and radiculopathy. PURPOSE The primary purpose of this study was to analyze if the DOS has any effect on clinical outcomes. STUDY DESIGN/SETTING A post hoc analysis was performed on an original prospective clinical study analyzing clinical outcomes and cervical sagittal alignment correlations. PATIENTS SAMPLE Fifty-eight patients undergoing one- or two-level ACDF surgeries for cervical degenerative radiculopathy were analyzed. OUTCOME MEASURES Standardized questionnaires were used to evaluate clinical outcomes. Neck and arm pain was evaluated using (Visual Analog Scale [VAS]). Two scales of Health-Related Quality-of-Life Questionnaire (Short-Form 36 Health Survey [SF-36]) were used for this study: the physical component summary (PCS) and mental component summary (MCS). Neck disability index (NDI) was used to evaluate chronic disability in activities of daily living. The patients completed a self-reported Patient Satisfaction with Results Survey. METHODS Patients who had previous or redo surgeries, were diagnosed with myelopathy or had more than two-level ACDF surgeries were excluded, leaving a total of 58 patients. The mean follow-up was 37.2 months (range 12-54). Patients were divided into two groups for clinical outcome analyses according to the DOS: patients who had surgery within 6 months (n=29) or more than 6 months (n=29) after becoming symptomatic. RESULTS There were no statistically significant differences in any demographic or clinical parameters among the patient groups. Controlling for preoperative scores, the patients who had surgery within 6 months reported significantly higher reduction (p=.04) in arm pain scores compared with the patients who waited more than 6 months. No significant differences were detected in postoperative neck pain VAS (p=.3), NDI (p=.06), SF-36 PCS (p=.08), and MCS (p=.8) scores. CONCLUSIONS Neck and upper extremity pain can be successfully treated conservatively. In those cases, when surgical intervention is pursued, patients with shorter DOS have better improvement in radiculopathy symptoms that is statistically significant.

Comparing vertebral body reconstruction implants for the treatment of thoracic and lumbar metastatic spinal tumors: a consecutive case series of 37 patients.

Study Design Retrospective case series. Objective To compare different interbody reconstruction implants after corpectomy in metastatic spine tumors. Summary of Background Data Vertebral body reconstruction after corpectomy is common for patients with metastatic spine tumors. Although various implants are reported individually in the literature, no study to-date has compared them with one another directly. Methods Thirty-seven consecutive patients with metastatic tumors of the thoracic or lumbar spine underwent single or multilevel corpectomy with subsequent interbody reconstruction. Longevity of interbody graft was primarily evaluated in this study as defined by the need for any revision surgeries or complications after surgery. Data was collected retrospectively. Results Twenty-seven, 5, and 5 patients underwent reconstruction with metal implants, bone implants, and polymethylmethacrylate (PMMA), respectively. Twenty-three patients had metastatic tumor involvement of the thoracic spine and 14 patients had tumor involvement of the lumbar spine. Three patients (8.1%) required additional surgery: 1 wound infection, 1 hardware revision, and 1 for resection of an intradural, intramedullary tumor not identified at the first operation. Overall complication rate was 43.2% (16 patients) and 2 patients died within 30 days of their index spine surgery. Postoperative complication rates were more than double in the metal implant group (52%) compared with an equal number of complications in bone (20%) and PMMA (20%) implant group. The rate of revision surgery was highest in the bone group (40%) compared with none in the PMMA and only 3.7% in the metal interbody groups. Conclusions Vertebral body reconstruction after corpectomy for patients with metastatic tumors to the thoracic and lumbar spine can be performed effectively with metal, bone, or cement implants. Although metal implants are used in the majority of reconstruction cases, they seem to have a higher rate of overall complications, with bone interbody constructs showing a higher rate of revision surgery.