Amgad S. Hanna

The Therapeutic Role of Interleukin-10 after Spinal Cord Injury

Spinal cord injury (SCI) is a devastating condition affecting 270,000 people in the United States. A potential treatment for decreasing the secondary inflammation, excitotoxic damage, and neuronal apoptosis associated with SCI, is the anti-inflammatory cytokine interleukin-10. The best characterized effects of IL-10 are anti-inflammatory-it downregulates pro-inflammatory species interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor-α, interferon-γ, matrix metalloproteinase-9, nitric oxide synthase, myeloperoxidase, and reactive oxygen species. Pro-apoptotic factors cytochrome c, caspase 3, and Bax are downregulated by IL-10, whereas anti-apoptotic factors B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X, B-cell lymphoma-extra large (Bcl-xl) are upregulated by IL-10. IL-10 also provides trophic support to neurons through the IL-10 receptor. Increased tissue sparing, functional recovery, and neuroprotection are seen with an immediate post-SCI systemic administration of IL-10. Treatment of SCI with IL-10 has been used successfully in combination with Schwann cell and olfactory glial cell grafts, as well as methylprednisolone. Minocycline, tetramethylpyrazine, and hyperbaric oxygen treatment all increase IL-10 levels in a SCI models and result in increased tissue sparing and functional recovery. A chronic systemic administration of IL-10 does not appear to be beneficial to SCI recovery and causes increased susceptibility to septicemia, pneumonia, and peripheral neuropathy. However, a localized upregulation of IL-10 has been shown to be beneficial and can be achieved by herpes simplex virus gene therapy, injection of poliovirus replicons, or surgical placement of a slow-release compound. IL-10 shows promise as a treatment for SCI, although research on local IL-10 delivery timeline and dosage needs to be expanded.

Inadvertent insertion of nasogastric tube into the brain stem and spinal cord after endoscopic skull base surgery

A significant number of neurosurgical patients require feeding tube placement via a nasogastric route. It is used as a temporary access for enteral feeding until patients are able to swallow or receive permanent access. Despite how commonly feeding tubes are used, they are not without potential complications. We report a case of inadvertent placement of small-bore feeding tube into the brain stem and spinal cord in a patient with a history of previous endoscopic transnasal resection of clival chordoma. We discuss the management of this complication and the strategies that have been developed to avoid this complication in the future.

Basic techniques for long distance axon tracing in the spinal cord.

The regeneration of axons after a spinal cord injury or disease is attracting a significant amount of interest among researchers. Being able to assess these axons in terms of morphology, length and origin is essential to our understanding of the regeneration process. Recently, two specific axon tracers have gained much recognition; biotinylated dextran amine (BDA) 10 kDa as an anterograde tracer and cholera toxin‐B as a retrograde tracer. However, there are still several complexities when using these tracers, including the volume that should be administered and the best administration site so that a significant amount of axons are labeled in the area of interest. In this article, we describe some simple procedures for injecting the tracers and detecting them. We also quantified the number of axons at different locations of the spinal cord. Our results show axons labeled from motor cortex injections traveled down to the lumbosacral spinal cord in 2 weeks, while BDA injections into the lateral vestibular nucleus and reticular formation took 3 weeks to label axons in the lumbosacral spinal cord. Moreover, this protocol outlines some basic procedures that could be used in any laboratory and gives insight into the number of axons labeled and how procedures could be tailored to meet specific researchers needs. Microsc. Res. Tech. 76:1240–1249, 2013.

Lateral femoral cutaneous nerve transposition: Renaissance of an old concept in the light of new anatomy

Meralgia paresthetica causes pain in the anterolateral thigh. Most surgical procedures involve nerve transection or decompression. We conducted a cadaveric study to determine the feasibility of lateral femoral cutaneous nerve (LFCN) transposition. In three cadavers, the LFCN was exposed in the thigh and retroperitoneum. The two layers of the LFCN canal superficial and deep to the nerve were opened. The nerve was then mobilized medially away from the ASIS, by cutting the septum medial to sartorius. It was possible to mobilize the nerve for 2 cm medial to the ASIS. The nerve acquired a much straighter course with less tension. A new technique of LFCN transposition is presented here as an anatomical feasibility study. The surgical technique is based on the new understanding of the LFCN canal. Clin. Anat. 30:409–412, 2017.

Sustained release of neurotrophin-3 via calcium phosphate-coated sutures promotes axonal regeneration after spinal cord injury.

Because of the dynamics of spinal cord injury (SCI), the optimal treatment will almost certainly be a combination approach to control the environment and promote axonal growth. This study uses peripheral nerve grafts (PNGs) as scaffolds for axonal growth while delivering neurotrophin‐3 (NT‐3) via calcium phosphate (CaP) coatings on surgical sutures. CaP coating was grown on sutures, and NT‐3 binding and release were characterized in vitro. Then, the NT‐3‐loaded sutures were tested in a complete SCI model. Rats were analyzed for functional improvement and axonal growth into the grafts. The CaP‐coated sutures exhibited a burst release of NT‐3, followed by a sustained release for at least 20 days. Functionally, the rats with PNGs + NT‐3‐loaded sutures and the rats treated with PNGs scored significantly higher than controls on day 56 postoperatively. However, functional scores in rats treated with PNGs + NT‐3‐loaded suture were not significantly different from those of rats treated with PNGs alone. Cholera toxin subunit B (CTB) labeling rostral to the graft was not observed in any controls, but CTB labeling rostral to the graft was observed in almost all rats that had had a PNG. Neurofilament labeling on transverse sections of the graft revealed that the rats treated with the NT‐3‐loaded sutures had significantly more axons per graft than rats treated with an NT‐3 injection and rats without NT‐3. These data demonstrate that PNGs serve as scaffolds for axonal growth after SCI and that CaP‐coated sutures can efficiently release NT‐3 to increase axonal regeneration.

Use of chemical shift encoded magnetic resonance imaging (CSE-MRI) for high resolution fat-suppressed imaging of the brachial and lumbosacral plexuses

PURPOSE In the era of increasingly complex surgical techniques for peripheral nerve repair, there is a need for high spatial resolution imaging of the neural plexuses in the body. We describe our experience with chemical shift encoded MRI and its implications for patient management. MATERIALS AND METHODS IDEAL water-fat separation is a chemical shift based method of homogeneously suppressing signal from fat, while maintaining adequate signal. This technique was used in clinical practice and the patient images reviewed. RESULTS IDEAL water-fat separation was shown to improve visualization of the brachial and lumbosacral plexuses with good fat suppression and high signal to noise ratio. CONCLUSION IDEAL water - fat separation is an excellent technique to use in the imaging of the brachial and lumbosacral plexuses as it balances the need for homogeneous fat suppression with maintenance of excellent signal to noise ratio.

Intraoperative ultrasound-assisted peripheral nerve surgery.

Historically, peripheral nerve surgery has relied on landmarks and fairly extensive dissection for localization of both normal and pathological anatomy. High-resolution ultrasonography is a radiation-free imaging modality that can be used to directly visualize peripheral nerves and their associated pathologies prior to making an incision. It therefore helps in localization of normal and pathological anatomy, which can minimize the need for extensive exposures. The authors found intraoperative ultrasound (US) to be most useful in the management of peripheral nerve tumors and neuromas of nerve branches that are particularly small or have a deep location. This study presents the use of intraoperative US in 5 cases in an effort to illustrate some of the applications of this useful surgical adjunct.

Transposition of the lateral femoral cutaneous nerve

OBJECTIVEMeralgia paresthetica causes pain, burning, and loss of sensation in the anterolateral thigh. Surgical treatment traditionally involves neurolysis or neurectomy of the lateral femoral cutaneous nerve (LFCN). After studying and publishing data on the anatomical feasibility of LFCN transposition, the author presents here the first case series of patients who underwent LFCN transposition.METHODSNineteen patients with meralgia paresthetica were treated in the Department of Neurological Surgery at University of Wisconsin between 2011 and 2016; 4 patients underwent simple decompression, 5 deep decompression, and 10 medial transposition. Data were collected prospectively and analyzed retrospectively. No randomization was performed. The groups were compared in terms of pain scores (based on a numeric rating scale) and reoperation rates.RESULTSThe numeric rating scale scores dropped significantly in the deep-decompression (p = 0.148) and transposition (p < 0.0001) groups at both the 3- and 12-month follow-up. The reoperation rates were significantly lower in the deep-decompression and transposition groups (p = 0.0454) than in the medial transposition group.CONCLUSIONSBoth deep decompression and transposition of the LFCN provide better results than simple decompression. Medial transposition confers the advantage of mobilizing the nerve away from the anterior superior iliac spine, giving it a straighter and more relaxed course in a softer muscle bed.

Lateral Femoral Cutaneous Nerve

The lateral femoral cutaneous nerve (LFCN) arises from L2–L3 posterior divisions. It exits the psoas muscle along its lateral border and then runs obliquely caudally and laterally towards the anterior superior iliac spine (ASIS ). It passes under the lateral part of the inguinal ligament to enter the thigh in its own sheath (a complete fascial tunnel surrounds the nerve). It supplies the skin of the anterolateral thigh.

Immunohistochemical assessment of rat nerve isografts and immunosuppressed allografts.

Objective: Autologous peripheral nerve grafts are commonly used clinically as a treatment for peripheral nerve injuries. However, in research using an autologous graft is not always feasible due to loss of function, which in many cases is assessed to determine the efficacy of the peripheral nerve graft. In addition, using allografts for research require the use of an immunosuppressant, which creates unwanted side effects and another variable within the experiment that can affect regeneration. The objective of this study was to analyze graft rejection in peripheral nerve grafts and the effects of cyclosporine A (CSA) on axonal regeneration. Methods: Peripheral nerve grafts in inbred Lewis rats were compared with Sprague-Dawley (SD) rats to assess graft rejection, CSA side effects, immune responses, and regenerative capability. Macrophages and CD8+ cells were labeled to determine graft rejection, and neurofilaments were labeled to determine axonal regeneration. Results: SD rats without CSA had significantly more macrophages and CD8+ cells compared to Lewis autografts, Lewis isografts, and SD allografts treated with CSA. Lewis autografts, Lewis isografts, and SD autografts had significantly more regenerated axons than SD rat allografts. Moreover, allografts in immunosuppressed SD rats had significantly less axons than Lewis rat autograft and isografts. Discussion: Autografts have long been the gold standard for treating major nerve injuries and these data suggest that even though CSA is effective at reducing graft rejection, axon regeneration is still superior in autografts versus immunosuppressed allografts.