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Wilson Z. Ray, Amy Lee, Spiros L. Blackburn, Gregg T. Lueder and Jeffrey R. Leonard

✓The authors report on an 8-month-old infant with an orbital capillary hemangioma. The patient had been treated with high-dose corticosteroid therapy and had had a recent decrease in dose. The patient presented to the emergency department with increased irritability and bulging fontanelles. On lumbar puncture the opening pressure was > 55 cm H2O. Ophthalmological examination revealed interval development of papilledema. The child was treated with high-volume lumbar puncture, subsequent drainage of 10 ml of cerebrospinal fluid, resumption of the previous steroid dose, and acetazolomide therapy. The patient's symptoms resolved and follow-up ophthalmological examination revealed interval resolution of papilledema. The authors present the youngest reported case of pseudotumor development after corticosteroid tapering.

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Wilson Z. Ray, Russel G. Strom, Spiros L. Blackburn, William W. Ashley Jr., Gregorio A. Sicard and Keith M. Rich

Object

The aim of this study was to determine the efficacy of venous ultrasonography in screening for deep venous thrombosis (DVT) after subarachnoid hemorrhage (SAH). A large cohort of patients who had suffered SAH was evaluated with the primary end points of ascertaining the incidence of asymptomatic DVT with venous Doppler ultrasonography screening and of identifying risk factors for the development of DVT and subsequent pulmonary embolism.

Methods

Data from patients with aneurysmal SAH who had been admitted to the neurosurgical intensive care unit (ICU) between December 2002 and October 2006 were retrospectively evaluated. Patients who had undergone surgical or endovascular treatment of an aneurysm following SAH and survived ≥ 15 days were included in the study.

Results

The overall incidence of DVT among the entire study cohort was 18%. A subgroup analysis identified all patients, with or without symptoms for DVT, who had undergone venous Doppler ultrasonography screening. The incidence of asymptomatic DVT was 24%. Univariate analysis of all patients revealed a significant correlation between the risk of DVT and Hunt and Hess grade (r = 0.38, p < 0.0001), Fisher grade (r = 0.31, p < 0.0001), total hospital stay (r = 0.49, p < 0.0001), and number of days in the ICU (r = 0.48, p < 0.0001). Multivariate analysis demonstrated that the total hospital stay and number of days in the ICU were significant predictors of DVT in all patients (p < 0.0001 and p < 0.0002, respectively). In the subgroup of screened patients, Hunt and Hess grade, total hospital stay, and number of days in the ICU were significant predictors of DVT. Although screened patients were more likely to have DVT (χ2 = 6.0976, p < 0.02), there was no significant difference in the incidence of DVT or pulmonary embolism between patients who did and those who did not undergo routine lower-extremity Doppler ultrasonography screening.

Conclusions

Routine compressive venous Doppler ultrasonography is an efficient, noninvasive means of identifying DVT as a screening modality in both symptomatic and asymptomatic patients following aneurysmal SAH. The ability to confirm or deny the presence of DVT in this patient population allows one to better identify the indications for chemoprophylaxis. Prophylaxis for venous thromboembolism in neurosurgical patients is common. Emerging literature and anecdotal experience have exposed risks of complications with prophylactic anticoagulation protocols. The identification of patients at high risk—for example, those with asymptomatic DVT—will allow physicians to better assess the role of prophylactic anticoagulation.

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James M. Johnston, David D. Limbrick Jr., Wilson Z. Ray, Stephanie Brown, Joshua Shimony and Tae Sung Park

Rosai-Dorfman disease (RDD) is an idiopathic histioproliferative disorder that rarely involves the CNS. Rosai-Dorfman disease is exceedingly rare in the pediatric population and has never been observed in the cerebellum of a child. The authors present the case of a 14-year-old male with a cerebellar lesion having radiographic characteristics of Lhermitte-Duclos disease. After a period of observation with a presumptive diagnosis of Lhermitte-Duclos disease, the child underwent suboccipital craniotomy and resection of the lesion due to continuous suboccipital headaches. Histological examination of the tissue demonstrated RDD. The published literature on RDD is reviewed with an emphasis on differential diagnosis.

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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

Object

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.

Methods

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.

Results

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.

Conclusions

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.

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Christina K. Magill, Amy M. Moore, Ying Yan, Alice Y. Tong, Matthew R. MacEwan, Andrew Yee, Ayato Hayashi, Daniel A. Hunter, Wilson Z. Ray, Philip J. Johnson, Alexander Parsadanian, Terence M. Myckatyn and Susan E. Mackinnon

Object

Glial cell line–derived neurotrophic factor (GDNF) has potent survival effects on central and peripheral nerve populations. The authors examined the differential effects of GDNF following either a sciatic nerve crush injury in mice that overexpressed GDNF in the central or peripheral nervous systems (glial fibrillary acidic protein [GFAP]–GDNF) or in the muscle target (Myo-GDNF).

Methods

Adult mice (GFAP-GDNF, Myo-GDNF, or wild-type [WT] animals) underwent sciatic nerve crush and were evaluated using histomorphometry and muscle force and power testing. Uninjured WT animals served as controls.

Results

In the sciatic nerve crush, the Myo-GDNF mice demonstrated a higher number of nerve fibers, fiber density, and nerve percentage (p < 0.05) at 2 weeks. The early regenerative response did not result in superlative functional recovery. At 3 weeks, GFAP-GDNF animals exhibit fewer nerve fibers, decreased fiber width, and decreased nerve percentage compared with WT and Myo-GDNF mice (p < 0.05). By 6 weeks, there were no significant differences between groups.

Conclusions

Peripheral delivery of GDNF resulted in earlier regeneration following sciatic nerve crush injuries than that with central GDNF delivery. Treatment with neurotrophic factors such as GDNF may offer new possibilities for the treatment of peripheral nerve injury.

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Oral Presentations

2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010

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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

Object

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.

Methods

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.

Results

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.

Conclusions

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.

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Spiros L. Blackburn, William W. Ashley Jr., Keith M. Rich, Joseph R. Simpson, Robert E. Drzymala, Wilson Z. Ray, Christopher J. Moran, DeWitte T. Cross III, Michael R. Chicoine, Ralph G. Dacey Jr., Colin P. Derdeyn and Gregory J. Zipfel

Object

Large cerebral arteriovenous malformations (AVMs) are often not amenable to direct resection or stereotactic radiosurgery (SRS) treatment. An alternative treatment strategy is staged endovascular embolization followed by SRS (Embo/SRS). The object of this study was to examine the experience at Washington University in St. Louis with Embo/SRS for large AVMs and review the results in earlier case series.

Methods

Twenty-one cases involving patients with large AVMs treated with Embo/SRS between 1994 and 2006 were retrospectively evaluated. The AVM size (before and after embolization), procedural complications, radiological outcome, and neurological outcome were examined. Radiological success was defined as AVM obliteration as demonstrated by catheter angiography, CT angiography, or MR angiography. Radiological failure was defined as residual AVM as demonstrated by catheter angiography, CT angiography, or MR angiography performed at least 3 years after SRS.

Results

The maximum diameter of all AVMs in this series was > 3 cm (mean 4.2 cm); 12 (57%) were Spetzler-Martin Grade IV or V. Clinical follow-up was available in 20 of 21 cases; radiological follow-up was available in 19 of 21 cases (mean duration of follow-up 3.6 years). Forty-three embolization procedures were performed; 8 embolization-related complications occurred, leading to transient neurological deficits in 5 patients (24%), minor permanent neurological deficits in 3 patients (14%), and major permanent neurological deficits in none (0%). Twenty-one SRS procedures were performed; 1 radiation-induced complication occurred (5%), leading to a permanent minor neurological deficit. Of the 20 patients with clinical follow-up, none experienced cerebral hemorrhage. In the 19 patients with radiological follow-up, AVM obliteration was confirmed by catheter angiography in 13, MR angiography in 2, and CT angiography in 1. Residual nidus was found in 3 patients. In patients with follow-up catheter angiography, the AVM obliteration rate was 81% (13 of 16 cases).

Conclusions

Staged endovascular embolization followed by SRS provides an effective means of treating large AVMs not amenable to standard surgical or SRS treatment. The outcomes and complication rates reported in this series compare favorably to the results of other reported therapeutic strategies for this very challenging patient population.

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Wilson Z. Ray, Mitchell A. Pet, Andrew Yee and Susan E. Mackinnon

Object

The clinical outcomes of patients with brachial plexus injuries who underwent double fascicular transfer (DFT) using fascicles from the median and ulnar nerves to reinnervate the biceps and brachialis muscles were evaluated.

Methods

The authors conducted a retrospective chart review of 29 patients with brachial plexus injuries that were treated with DFT for restoration of elbow flexion. All patients underwent pre- and postoperative clinical evaluation using the Medical Research Council grading system.

Results

The mean patient age was 37 years (range 17–68 years), and there was a mean follow-up of 19 ± 12 months (range 8–68 months). At the most recent follow-up, all but 1 patient (97%) had regained elbow flexion. Eight patients recovered Grade M5, 15 patients recovered Grade M4, and 4 patients recovered Grade M3 elbow flexion strength. There was no evidence of functional deficit in the donor nerve distributions.

Conclusions

Study results demonstrated the reliable restoration of M4–M5 elbow flexion following double fascicular transfer in patients with brachial plexus injuries.

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Wilson Z. Ray, Mitchell A. Pet, Michael C. Nicoson, Andrew Yee, Lorna C. Kahn and Susan E. Mackinnon

The authors report a case of long thoracic nerve (LTN) palsy treated with two-level motor nerve transfers of a pectoral fascicle of the middle trunk, and a branch of the thoracodorsal nerve. This procedure resulted in near-total improvement of the winged scapula deformity, and a return of excellent shoulder function. A detailed account of the postoperative physical therapy regimen is included, as this critical component of the favorable result cannot be overlooked. This case establishes the two-level motor nerve transfer as a new option for treating LTN palsy, and demonstrates that nerve transfers should be considered in the therapeutic algorithm of an idiopathic mononeuritis.