Juan Valdivia

Surgical treatment of peripheral neuropathy: outcomes from 100 consecutive decompressions.

Since 1992 it has been reported that patients with diabetes mellitus recover sensibility and obtain relief of pain from neuropathy symptoms by decompression of lower-extremity peripheral nerves. None of these reports included a series with more than 36 diabetic patients with lower-extremity nerves decompressed, and only recently has a single report appeared of the results of this approach in patients with nondiabetic neuropathy. No previous report has described a change in balance related to restoration of sensibility. A prospective study was conducted of 100 consecutive patients (60 with diabetes and 40 with idiopathic neuropathy) operated on by a single surgeon, other than the originator of this approach, and with the postoperative results reviewed by someone other than these two surgeons. Each patient had neurolysis of the peroneal nerve at the knee and the dorsum of the foot, and the tibial nerve released in the four medial ankle tunnels. After at least 1 year of follow-up, 87% of patients with preoperative numbness reported improved sensation, 92% with preoperative balance problems reported improved balance, and 86% whose pain level was 5 or greater on a visual analog scale from 0 (no pain) to 10 (the most severe pain) before surgery reported an improvement in pain. Decompression of compressed lower-extremity nerves improves sensation and decreases pain, and should be recommended for patients with neuropathy who have failed to improve with traditional medical treatment.

BMP-2 inhibits the tumorigenicity of cancer stem cells in human osteosarcoma OS99-1 cell line

Previously, based on high ALDH activity, we showed that cancer stem cells (CSCs) could be identified as ALDHbr cells from an aggressive human osteosarcoma OS99-1 cell line. In this study, we evaluate the impact of BMP-2 on CSCs.Three types of BMP receptors were expressed in freshly sorted ALDHbr cells. In vitro, growth of the sorted ALDHbr cells was inhibited by BMP-2. Using RT-PCR analysis, BMP-2 was found to down-regulate the expression of embryonic stem cell markers Oct3/4, Nanog, and Sox-2, and up-regulate the transcription of osteogenic markers Runx-2 and Collagen Type I. In vivo, all animals receiving ALDHbr cells treated with BMP-2 did not form significant tumors, while untreated ALDHbr cells developed large tumor masses in NOD/SCID mice. Immunostaining confirmed few Ki-67 positive cells were present in the sections of tumor containing ALDHbr cells treated with BMP-2. These results suggest that BMP-2 suppresses tumor growth by reducing the gene expression of tumorigenic factors and inducing the differentiation of CSCs in osteosarcoma. BMP-2 or BMP-2-mimetic drugs, if properly delivered to tumor and combined with traditional therapies, may therefore provide a new therapeutic option for treatment of osteosarcoma.

Complication avoidance and management in anterior lumbar interbody fusion.

The goal of this study was to review the literature to compare strategies for avoiding and treating complications from anterior lumbar interbody fusion (ALIF), and thus provide a comprehensive aid for spine surgeons. A thorough review of databases from the US National Library of Medicine and the National Institutes of Health was conducted. The complications of ALIF addressed in this paper include pseudarthrosis and subsidence, vascular injury, retrograde ejaculation, ileus, and lymphocele (chyloretroperitoneum). Strategies identified for improving fusion rates included the use of frozen rather than freeze-dried allograft, cage instrumentation, and bone morphogenetic protein. Lower cage heights appear to reduce the risk of subsidence. The most common vascular injury is venous laceration, which occurs less frequently when using nonthreaded interbody grafts such as iliac crest autograft or femoral ring allograft. Left iliac artery thrombosis is the most common arterial injury, and its occurrence can be minimized by intermittent release of retraction intraoperatively. The risk of retrograde ejaculation is significantly higher with laparoscopic approaches, and thus should be avoided in male patients. Despite precautionary measures, complications from ALIF may occur, but treatment options do exist. Bowel obstruction can be treated conservatively with neostigmine or with decompression. In cases of postoperative lymphocele, resolution can be attained by creating a peritoneal window. By recognizing ways to minimize complications, the spine surgeon can safely use ALIF procedures.

Schmorl's nodes.

IntroductionFirst described in 1927, a Schmorl’s node (SN) is the herniation of nucleus pulposus (NP) through the cartilaginous and bony end plate into the body of the adjacent vertebra. SNs are common findings on imaging, and although most SNs are asymptomatic, some have been shown to become painful lesions. In this manuscript, we review the literature regarding the epidemiology, clinical presentation, pathogenesis, imaging, and management of SNs.Materials and methods Using databases from the US National Library of Medicine and the National Institutes of Health, relevant articles were identified.Results While several theories regarding the pathogenesis of SNs have been proposed, an axial load model appears to have the greatest supporting evidence. Symptomatic SNs are thought to be due to the inflammatory response solicited by the herniation of NP into the well-vascularized vertebral body. Management options for symptomatic SNs vary, ranging from medical management to surgical fusion.ConclusionSNs are common lesions that are often asymptomatic. In certain cases, SNs can cause back pain. No consensus on pathogenesis exists. There is no established treatment modality for symptomatic SNs.

Chemotactic and mitogenic stimuli of neuronal apoptosis in patients with medically intractable temporal lobe epilepsy

To identify the upstream signals of neuronal apoptosis in patients with medically intractable temporal lobe epilepsy (TLE), we evaluated by immunohistochemistry and confocal microscopy brain tissues of 13 TLE patients and 5 control patients regarding expression of chemokines and cell-cycle proteins. The chemokine RANTES (CCR5) and other CC-chemokines and apoptotic markers (caspase-3, -8, -9) were expressed in lateral temporal cortical and hippocampal neurons of TLE patients, but not in neurons of control cases. The chemokine RANTES is usually found in cytoplasmic and extracellular locations. However, in TLE neurons, RANTES was displayed in an unusual location, the neuronal nuclei. In addition, the cell-cycle regulatory transcription factor E2F1 was found in an abnormal location in neuronal cytoplasm. The pro-inflammatory enzyme cyclooxygenase-2 and cytokine interleukin-1β were expressed both in neurons of patients suffering from temporal lobe epilepsy and from cerebral trauma. The vessels showed fibrin leakage, perivascular macrophages and expression of IL-6 on endothelial cells. In conclusion, the cytoplasmic effects of E2F1 and nuclear effects of RANTES might have novel roles in neuronal apoptosis of TLE neurons and indicate a need to develop new medical and/or surgical neuroprotective strategies against apoptotic signaling by these molecules. Both RANTES and E2F1 signaling are upstream from caspase activation, thus the antagonists of RANTES and/or E2F1 blockade might be neuroprotective for patients with medically intractable temporal lobe epilepsy. The results have implications for the development of new medical and surgical therapies based on inhibition of chemotactic and mitogenic stimuli of neuronal apoptosis in patients with medically intractable temporal lobe epilepsy.

Surgical treatment of superimposed, lower extremity, peripheral nerve entrapments with diabetic and idiopathic neuropathy.

BackgroundAlthough it is recognized that people with peripheral neuropathy have an increased prevalence of chronic nerve entrapment, controversy still exists over their management. The present report details the evaluation, surgical approach, and outcome of a large cohort of people with diabetic and with idiopathic neuropathy. MethodsA retrospective review of 158 consecutive patients, 96 with diabetic and 62 with idiopathic neuropathy, was done to analyze the results of neurolysis of multiple sites of chronic nerve compression in the lower extremity. Of these patients, 50 had a contralateral limb decompressed for a total of 208 limbs included in the study. Outcomes included visual analog scale (VAS) for pain in the 109 patients who had pain level greater than 8.0, measurement of the cutaneous pressure threshold for sensibility, self-reported change in pain medication usage, and self-reported change in balance. ResultsWith a minimum follow-up of 1 year, 88% of patients with preoperative numbness reported improvement in sensation (P < 0.001). Of the 84 patients with impaired balance, 81% reported improvement in balance. Of those whose VAS was greater than 8, 83% reported an improvement in VAS (P < 0.001). There was a concomitant reduction in pain medication usage. There was no difference in outcomes between patients with diabetic versus idiopathic neuropathy in response to nerve decompression. ConclusionsNeurolysis of lower extremity chronic nerve compressions in patients with neuropathy and superimposed nerve compressions is an effective method for relieving pain, restoring sensation, and improving balance.

Reliability of the clinical examination in the diagnosis of neurogenic versus vascular claudication

BACKGROUND CONTEXT As research increasingly challenges the diagnostic accuracy of advanced imaging for lumbar spinal stenosis, the impression gleaned from the office evaluation becomes more important. Neurogenic claudication is a hallmark of lumbar spinal stenosis, but the reliability of clinical impression of claudication has not been studied. PURPOSE To determine the reliability of the clinical examination for neurogenic claudication in an idealized setting. STUDY DESIGN Prospective masked controlled trial. PATIENT SAMPLE Persons aged 55 to 90 years were recruited to form three groups: those offered surgery for spinal stenosis by academic spine surgeons, those who had peripheral vascular symptoms and positive ankle-brachial index (ABI), and those who were asymptomatic. All were extensively screened against confounding diseases. Forty-three neurogenic, 12 vascular, and 35 asymptomatic recruits were tested. OUTCOME MEASURES Clinical impression of neurogenic claudication. METHODS A neurosurgeon and a vascular surgeon, masked to each others findings, imaging, and recruitment status, performed a codified but unconstrained comprehensive spine and vascular history and physical examination for each subject. The surgeons impression was recorded. RESULTS Masked surgeons strongly agreed with the recruitment diagnosis (neurosurgeon kappa 0.761, vascular surgeon kappa 0.803, both p<.001) and with each other (kappa 0.717, p<.001). However, disagreements did occur between examiners and recruitment diagnosis (neurosurgeon n=13 cases, vascular surgeon n=10) and between examiners (n=14 cases). Pain level and marginally some measures of disability related to the agreement, but specific aspects of the physical examination, showed poor interrater reliability and did not contribute to the agreement. CONCLUSIONS The clinical impression of neurogenic claudication is a reliable construct. The history, but not the poorly reproduced physical examination, contributes to reliability. The level of disagreement between experts in this simplified, yet severely involved, population raises concern about the risk of misdiagnosis in individual cases. Thus, surgical and other consequential decisions about diagnosis may require ancillary tests such as electromyography or ABI.

A novel murine model of human renal cell carcinoma spinal metastasis

There is currently no reproducible animal model of renal cell carcinoma (RCC) spinal metastasis that allows for laboratory study of the human disease. In this report, we describe an animal model that reliably reproduces RCC spinal metastasis using a human tumor cell line. A posterior surgical approach was used to implant tumor cells into the lamina of immunosuppressed mice. Histology sections were analyzed 12 weeks after tumor cell implantation to quantify the location and extent of tumor growth. RCC xenografts grew in treated animals (8 mice) with a reproducible pattern of growth. After implantation, tumor growth occurred primarily in the antero-posterior dimension. At 8 weeks after tumor cell implantation, there was visible tumor growth in all treated mice. Histologic correlation at 12 weeks after tumor cell implantation confirmed tumor growth involving primarily the paraspinal region and lamina. Our investigation resulted in an orthotopic model of human RCC spinal metastasis. Ultimately this will allow testing of targeted therapies for RCC with spinal involvement. Furthermore, this model can be expanded to develop similar spinal metastasis models for other tumor cell lines.

Pineal region myeloid sarcoma

The overwhelming majority of pineal region tumors are malignant germ cell tumors, pineal cell tumors, or glial tumors. To our knowledge we report the first patient with myeloid sarcoma in the pineal region. Myeloid sarcomas are composed of immature granulocytic precursor cells and are associated with acute myelogenous leukemia. Thus, myeloid sarcoma should be considered in the differential diagnosis of pineal region masses in patients with a known history of acute myelogenous leukemia.

Poster 146: The Reliability of the Clinical Diagnosis in Persons Offered Surgery for Lumbar Spinal Stenosis

Disclosures: M. Fredericson, Coolsystems, Inc, Consulting fees or other remuneration. Objective: To test the hypothesis that measures of patellar maltracking, tilt, and bisect offset, correlate with vastus medialis onset delays in patellofemoral pain (PFP) subjects classified as maltrackers. Design: Post hoc cohort study. Setting: Three-dimensional motion analysis laboratory, magnetic resonance (MR) imaging laboratory. Participants: 55 subjects: 15 healthy controls and 40 subjects with patellofemoral pain (PFP). Interventions: Not applicable. Main Outcome Measures: Correlations between electromyography (EMG) activation onset delay of vastus medialis (VM) muscle compared with vastus lateralis and patellar maltracking measures, tilt, and bisect offset. The subjects with PFP were classified into nonmaltrackers and maltrackers based on their tilt and bisect offset measurements. Anticipatory EMG activations during the swing phase of walking were analyzed. Tilt and bisect offset were measured from images acquired in an open-configuration MR scanner with a subject upright and the knee near full extension. Results: Subjects classified as maltrackers with both abnormal tilt and abnormal bisect offset demonstrated a significant relationship between VM onset delay and patellar tilt (R2 0.89, P .001). Approximately 38% of the PFP subjects (15 of 40) were classified as maltrackers, with 8 subjects having both abnormal tilt and abnormal bisect offset. Conclusions: The etiology of PFP is unclear. It has been theorized that delay in VM activity onset causes lateral maltracking of the patella, resulting in elevated stress and pain in the PF joint; however, evidence relating muscle onset delay to maltracking of the patella is sparse. The results of this study demonstrate a significant relationship between VM onset delay and patellar maltracking in subjects classified as maltrackers with both abnormal tilt and abnormal bisect offset. This implies that a clinical intervention such as VM retraining may be effective only in a subset of subjects with PFP, those with excessive tilt and excessive bisect offset measures.