✓ Two cases of sixth cranial nerve schwannoma are presented with a review of four other cases from the literature. The clinical spectrum, neuroradiological findings, and surgical outcome of the six cases are discussed. There are two distinct clinical presentations for sixth cranial nerve schwannomas. Type I sixth nerve schwannomas present with sixth nerve palsy and diplopia and arise from the cavernous sinus. In contrast, type II sixth nerve schwannomas have a more severe presentation with obstructive hydrocephalus, raised intracranial pressure, sixth nerve palsy, and diplopia. This type arises along the course of the sixth cranial nerve in the prepontine area. Cavernous sinus involvement in either type may preclude total surgical excision and indicate an increased possibility for recurrence.
Report of two cases
Howard Tung, Thomas Chen and Martin H. Weiss
Thomas H. Tung, Christine B. Novak and Susan E. Mackinnon
Object. In this study the authors evaluated the outcome in patients with brachial plexus injuries who underwent nerve transfers to the biceps and the brachialis branches of the musculocutaneous nerve.
Methods. The charts of eight patients who underwent an ulnar nerve fascicle transfer to the biceps branch of the musculocutaneous nerve and a separate transfer to the brachialis branch were retrospectively reviewed. Outcome was assessed using the Medical Research Council (MRC) grade to classify elbow flexion strength in conjunction with electromyography (EMG).
The mean patient age was 26.4 years (range 16–45 years) and the mean time from injury to surgery was 3.8 months (range 2.5–7.5 months). Recovery of elbow flexion was MRC Grade 4 in five patients, and Grade 4+ in three. Reinnervation of both the biceps and brachialis muscles was confirmed on EMG studies. Ulnar nerve function was not downgraded in any patient.
Conclusions. The use of nerve transfers to reinnervate the biceps and brachialis muscle provides excellent elbow flexion strength in patients with brachial plexus nerve injuries.
Susan E. Mackinnon, Brandon Roque and Thomas H. Tung
✓The purpose of this study is to report a surgical technique of nerve transfer to restore radial nerve function after a complete palsy due to a proximal injury to the radial nerve. The authors report the case of a patient who underwent direct nerve transfer of redundant or expendable motor branches of the median nerve in the proximal forearm to the extensor carpi radialis brevis and the posterior interosseous branches of the radial nerve. Assessment included degree of recovery of wrist and finger extension, and median nerve function including pinch and grip strength.
Clinical evidence of reinnervation was noted at 6 months postoperatively. The follow-up period was 18 months. Recovery of finger and wrist extension was almost complete with Grade 4/5 strength. Pinch and grip strength were improved postoperatively. No motor or sensory deficits related to the median nerve were noted, and the patient is very satisfied with her degree of functional restoration.
Transfer of redundant synergistic motor branches of the median nerve can successfully reinnervate the finger and wrist extensor muscles to restore radial nerve function. This median to radial nerve transfer offers an alternative to nerve repair, graft, or tendon transfer for the treatment of radial nerve palsy.
Thomas H. Tung, Christine B. Novak and Susan E. Mackinnon
In this study the authors evaluated the outcome in patients with brachial plexus injuries who underwent nerve transfers to the biceps and the brachialis branches of the musculocutaneous nerve.
The charts of eight patients who underwent an ulnar nerve fascicle transfer to the biceps branch of the musculocutaneous nerve and a separate transfer to the brachialis branch were retrospectively reviewed. Outcome was assessed using the Medical Research Council (MRC) grade to classify elbow flexion strength in conjunction with electromyography (EMG).
The mean patient age was 26.4 years (range 16–45 years) and the mean time from injury to surgery was 3.8 months (range 2.5–7.5 months). Recovery of elbow flexion was MRC Grade 4 in five patients, and Grade 4+in three. Reinnervation of both the biceps and brachialis muscles was confirmed on EMG studies. Ulnar nerve function was not downgraded in any patient.
The use of nerve transfers to reinnervate the biceps and brachialis muscle provides excellent elbow flexion strength in patients with brachial plexus nerve injuries.
Amy M. Moore, Emily M. Krauss, Rajiv P. Parikh, Michael J. Franco and Thomas H. Tung
Sciatic nerve injuries cause debilitating functional impairment, particularly when the injury mechanism and level preclude reconstruction with primary grafting. The purpose of this study was to demonstrate the anatomical feasibility of nerve transfers from the distal femoral nerve terminal branches to the tibial nerve and to detail the successful restoration of tibial function using the described nerve transfers.
Six cadaveric legs were dissected for anatomical analysis and the development of tension-free nerve transfers from femoral nerve branches to the tibial nerve. In 2 patients with complete tibial and common peroneal nerve palsies following sciatic nerve injury, terminal branches of the femoral nerve supplying the vastus medialis and vastus lateralis muscles were transferred to the medial and lateral gastrocnemius branches of the tibial nerve. Distal sensory transfer of the saphenous nerve to the sural nerve was also performed. Patients were followed up for lower-extremity motor and sensory recovery up to 18 months postoperatively.
Consistent branching patterns and anatomical landmarks were present in all dissection specimens, allowing for reliable identification, neurolysis, and coaptation of donor femoral and saphenous nerve branches to the recipients. Clinically, the patients obtained Medical Research Council Grade 3 and 3+ plantar flexion by 18 months postoperatively. Improved strength was accompanied by improved ambulation in both patients and by a return to competitive sports in 1 patient. Sensory recovery was demonstrated by an advancing Tinel sign in both patients.
This study illustrates the clinical success and anatomical feasibility of femoral nerve to tibial nerve transfers after proximal sciatic nerve injury.
Case report and review of the literature
Thomas H. Tung, D. Zachary Martin, Christine B. Novak, Carl Lauryssen and Susan E. Mackinnon
P Neurological injury to the lumbosacral plexus associated with pelvic and sacral fractures has traditionally been treated conservatively, despite significant and often debilitating functional deficits of the lower extremities. The authors report a case of reconstruction of the lumbosacral plexus, including nerve grafting to restore lower-extremity function caused by severe trauma to the pelvis. A 16-year-old boy sustained pelvic and sacral fractures in a motor vehicle accident. After stabilization of his orthopedic injuries, he suffered from paresis of his right gluteal and hamstring muscles and had no motor or sensory function below his knee. Two months later, he underwent reconstruction of his lumbosacral plexus performed using a nerve graft from his L-5 and S-1 nerve roots proximal to the inferior gluteal nerve and distal to a branch to the hamstring muscles. After another 2 months, his recovering saphenous nerve was transferred to the sensory component of the posterior tibial nerve by using cabled sural nerve grafts to restore sensation to the sole of his foot. After 2.5 years, he experienced reinnervation of his gluteal and hamstring muscles and could perceive vibration on the sole of his foot. With the assistance of a foot-drop splint, the patient ambulates well and is able to ski. Operative details and the relevant literature are reviewed.
Wilson Z. Ray, Santosh S. Kale, Rahul Kasukurthi, Esther M. Papp, Philip J. Johnson, Katherine B. Santosa, Ying Yan, Daniel A. Hunter, Susan E. Mackinnon and Thomas H. Tung
Nerve allotransplantation provides a temporary scaffold for host nerve regeneration and allows for the reconstruction of significant segmental nerve injuries. The need for systemic immunosuppression, however, limits the current clinical utilization of nerve allografts, although this need is reduced by the practice of cold nerve allograft preservation. Activation of T cells in response to alloantigen presentation occurs in the context of donor antigen presenting cells (direct pathway) or host antigen-presenting cells (indirect pathway). The relative role of each pathway in eliciting an alloimmune response and its potential for rejection of the nerve allograft model has not previously been investigated. The objective of this investigation was to study the effect of progressive periods of cold nerve allograft preservation on antigen presentation and the alloimmune response.
The authors used wild type C57Bl/6 (B6), BALB/c, and major histocompatibility Class II–deficient (MHC−/−) C57Bl/6 mice as both nerve allograft recipients and donors. A nonvascularized nerve allograft was used to reconstruct a 1-cm sciatic nerve gap. Progressive cold preservation of donor nerve allografts was used. Quantitative assessment was made after 3 weeks using nerve histomorphometry.
The donor-recipient combination lacking a functional direct pathway (BALB/c host with MHC−/− graft) rejected nerve allografts as vigorously as wild-type animals. Without an intact indirect pathway (MHC−/− host with BALB/c graft), axonal regeneration was improved (p < 0.052). One week of cold allograft preservation did not improve regeneration to any significant degree in any of the donor-recipient combinations. Four weeks of cold preservation did improve regeneration significantly (p < 0.05) for all combinations compared with wild-type animals without pretreatment. However, only in the presence of an intact indirect pathway (no direct pathway) did 4 weeks of cold preservation improve regeneration significantly compared with 1 week and no preservation in the same donorrecipient combination.
The indirect pathway may be the predominant route of antigen presentation in the unmodified host response to the nerve allograft. Prolonged duration of cold nerve allograft preservation is required to significantly attenuate the rejection response. Cold preservation for 4 weeks improves nerve regeneration with a significant effect on indirect allorecognition.
Wilson Z. Ray, Rahul Kasukurthi, Esther M. Papp, Amy M. Moore, Andrew Yee, Daniel A. Hunter, Nancy L. Solowski, Thalachallour Mohanakumar, Susan E. Mackinnon and Thomas H. Tung
Peripheral nerve allografts provide a temporary scaffold for host nerve regeneration and allow for the repair of significant segmental nerve injuries. Despite this potential, nerve allograft transplantation requires temporary systemic immunosuppression. Characterization of the immunological mechanisms involved in the induction of immune hyporesponsiveness to prevent nerve allograft rejection will help provide a basis for optimizing immunomodulation regimens or manipulating donor nerve allografts to minimize or eliminate the need for global immunosuppression.
The authors used C57Bl/6 mice and STAT4 and STAT6 gene BALB/c knockout mice. A nonvascularized nerve allograft was used to reconstruct a 1-cm sciatic nerve gap in the murine model. A triple costimulatory blockade of the CD40, CD28/B7, and inducible costimulatory (ICOS) pathways was used. Quantitative assessment was performed at 3 weeks with nerve histomorphometry, walking track analysis, and the enzyme-linked immunospot assay.
The STAT6 −/− mice received 3 doses of costimulation-blocking antibodies and had axonal regeneration equivalent to nerve isografts, while treated STAT4 −/− mice demonstrated moderate axonal regeneration but inferior to the T helper cell Type 2–deficient animals. Enzyme-linked immunospot assay analysis demonstrated a minimal immune response in both STAT4 −/− and STAT6 −/− mice treated with a costimulatory blockade.
The authors' findings suggest that Type 1 T helper cells may play a more significant role in costimulatory blockade–induced immune hyporesponsiveness in the nerve allograft model, and that Type 2 T helper differentation may represent a potential target for directed immunosuppression.
Russell R. Lonser, Stuart Walbridge, Alexander O. Vortmeyer, Svetlana D. Pack, Tung T. Nguyen, Nitin Gogate, Jeffery J. Olson, Aytac Akbasak, R. Hunt Bobo, Thomas Goffman, Zhengping Zhuang and Edward H. Oldfield
Object. To determine the acute and long-term effects of a therapeutic dose of brain radiation in a primate model, the authors studied the clinical, laboratory, neuroimaging, molecular, and histological outcomes in rhesus monkeys that had received fractionated whole-brain radiation therapy (WBRT).
Methods. Twelve 3-year-old male primates (Macaca mulatta) underwent fractionated WBRT (350 cGy for 5 days/week for 2 weeks, total dose 3500 cGy). Animals were followed clinically and with laboratory studies and serial magnetic resonance (MR) imaging. They were killed when they developed medical problems or neurological symptoms, lesions appeared on MR imaging, or at study completion. Gross, histological, and molecular analyses were then performed.
Nine (82%) of 11 animals that underwent long-term follow up (> 2.5 years) developed neurological symptoms and/or enhancing lesions on MR imaging, which were defined as glioblastoma multiforme (GBM), 2.9 to 8.3 years after radiation therapy. The GBMs were categorized as either unifocal (three) or multifocal (six), and were located in the supratentorial (six), infratentorial (two), or both (one) cranial regions. Histological examination revealed distant, noncontiguous tumor invasion within the white matter of all nine animals harboring GBMs. Novel interspecies comparative genomic hybridization (three animals) uniformly showed deletions in the GBMs that corresponded to chromosome 9 in humans.
Conclusions. The high rate of GBM formation (82%) following a therapeutic dose of WBRT in nonhuman primates indicates that radioinduction of these neoplasms as a late complication of this therapy may occur more frequently than is currently recognized in human patients. The development of these tumors while monitoring the monkeys' conditions with clinical and serial MR imaging studies, and access to the tumor and the entire brain for histological and molecular analyses offers an opportunity to gather unique insights into the nature and development of GBMs.