MPNSTs are rare malignancies that are classically associated with pre-existing plexiform neurofibromas in neurofibromatosis type 1 (NF-1) patients, but also occur in association with radiation as well as sporadically in patients with no known risk factors. The typical presentation of sporadic MPNST is a new painless enlarging mass. The typical presentation of MPNST in an NF-1 patient is rapid enlargement or new onset of pain associated with a pre-existing plexiform neurofibroma. Although both MPNST and benign neurofibromas share in common the absence of neurofibromin function due to loss of both NF-1 alleles, malignant transformation to MPNST requires several additional aberrations, most notably constituent activity of the proliferative Ras GTPase pathway, increased expression of growth factor receptors such as EGFR and decreased activity in additional tumor suppressors such as p53, p16INK4A and p19ARF. Grossly, MPNSTs typically appear "fusiform" (wide in the middle with tapering at both ends), larger than 5 cm and tan-gray on cut section. Necrosis, cyst formation and a "pseudocapsule" are frequently, but not always, present features. They may or may not be surrounded by portions of a pre-existing neurofibroma which have not undergone malignant transformation. The histologic features of MPNSTs show considerable variation and they overlap greatly with benign neurofibromas. However, several features argue in favor of MPNST, including perivascular hypercellularity, hyperchromatic wavy nuclei, high mitotic activity, necrosis and only focal or no areas of S-100 positivity. MRI is the imaging modality of choice for evaluating MPNSTs. It can be useful for differentiating MPNST from benign neurofibroma based on the absence of the fascicular sign, target sign and split-fat sign. CT is most useful for detecting metastases and chest CT should be ordered for all newly diagnosed patients due to the high incidence of pulmonary metastases at the time of presentation. PET-CT has an evolving role, especially with regards to differentiating neurofibroma from MPNST based on standardized uptake value (SUV). Prognostic factors for MPNST include tumor size, local recurrence and completeness of surgical resection. There is some evidence to suggest that tumor location (extremity vs. trunk, head and neck), histologic grade, p53 expression, S-100 expression, radiation therapy and histologic subtype may also be important prognostic factors. Complete surgical tumor removal provides the only hope for cure of MPNST. There have been some cases reported where neoadjuvant radiation and/or chemotherapy have allowed for subsequent complete surgical removal and thereby enabled cure. There is considerable evidence to suggest that adjuvant radiation, but not adjuvant chemotherapy, is helpful in preventing local recurrence of MPNST. Postoperative follow-up strategies for MPNST vary greatly across practitioners. No formal guidelines for follow-up have been proposed, however one author has demonstrated that regular, frequent re-evaluation every few months with MRI can allow for timely excision of local recurrences, thereby prolonging overall survival and in some cases even extending the potential for cure.

In this presentation, I attempt to define MPNST as a clinical entity and summarize much of the current state of knowledge on the pathogenesis, gross pathology, microscopic pathology, diagnostic imaging features and treatment strategies for MPNST.

Methods: We performed a multicenter, international, prospective cohort study (Surgical Timing in Acute Spinal Cord Injury Study: STASCIS) in adults aged 16–80 with cervical SCI. Enrolment occurred between 2002 and 2009 at 6 North American centers. The primary outcome was ordinal change in ASIA Impairment Scale (AIS) grade at 6 months follow-up. Secondary outcomes included assessments of complications rates and mortality.

Findings: A total of 313 patients with acute cervical SCI were enrolled. Of these, 182 underwent early surgery, at a mean of 14.2(65.4) hours, with the remaining 131 having late surgery, at a mean of 48.3(629.3) hours. Of the 222 patients with follow-up available at 6 months post injury, 19.8% of patients undergoing early surgery showed a $2 grade improvement in AIS compared to 8.8% in the late decompression group (OR = 2.57, 95% CI:1.11,5.97). In the multivariate analysis, adjusted for preoperative neurological status and steroid administration, the odds of at least a 2 grade AIS improvement were 2.8 times higher amongst those who underwent early surgery as compared to those who underwent late surgery (OR = 2.83, 95% CI:1.10,7.28). During the 30 day post injury period, there was 1 mortality in both of the surgical groups. Complications occurred in 24.2% of early surgery patients and 30.5% of late surgery patients (p = 0.21).

Conclusion: Decompression prior to 24 hours after SCI can be performed safely and is associated with improved neurologic outcome, defined as at least a 2 grade AIS improvement at 6 months follow-up.

OBJECTIVE: To demonstrate that DBS of the NAcc is an effective treatment modality for depression and that chemical and structural changes associated with these behavioral changes are markers of neuroplasticity.

METHODS: A deep brain stimulator was placed in the NAcc of male Wistar-Kyoto rats. Groups were divided into sham (no stimulation), intermittent (3 h/d for 2 weeks), or continuous (constant stimulation for 2 weeks). Exploratory and anxietylike behaviors were evaluated with the open-field test before and after stimulation. Tissue samples of the prefrontal cortex (PFC) were processed with Western blot analysis of markers of noradrenergic activity that included the noradrenergic synthesizing enzyme tyrosine hydroxylase. Analysis of tissue levels for catecholamines was achieved with high-performance liquid chromatography. Morphological properties of cortical pyramidal neurons were assessed with Golgi-Cox staining.

RESULTS: Subjects undergoing intermittent and continuous stimulation of the NAcc exhibited an increase in exploratory behavior and reduced anxietylike behaviors. Tyrosine hydroxylase expression levels were decreased in the PFC after intermittent and continuous DBS, and dopamine and norepinephrine levels were decreased after continuous stimulation. Golgi-Cox staining indicated that DBS increased the length of apical and basilar dendrites in pyramidal neurons of the PFC.

CONCLUSION: Deep brain stimulation induces behavioral improvement in and neurochemical and morphological alterations of the PFC that demonstrate changes within the circuitry of the brain different from the target area of stimulation. This observed dendritic plasticity may underlie the therapeutic efficacy of this treatment.

Methods: A retrospective review was performed of 387 SCS surgeries among 259 patients which included 167 new stimulator implantation to determine whether first time awake surgery for placement of spinal cord stimulators is preferable to non-awake placement.

Results: The incidence of device failure for patients implanted using neurophysiologically-guided placement under general anesthesia was one-half that for patients implanted awake (14.94% vs 29.7%).

Conclusion: Non-awake surgery is associated with fewer failure rates and therefore fewer re-operations, making it a viable alternative. Any benefits of awake implantation should carefully be considered in the future.

Objective: Prehospital use of antiplatelet agents has been associated with an increased risk for ICH as well as a secondary increase in ICH volume after the initial hemorrhage. Strategies to reestablish platelet aggregation are used in clinical practice, but without any established guidelines or recommendations. This article serves to evaluate the literature regarding “reversal” of antiplatelet agents in neurosurgical populations.

Methods: PUBMED and MEDLINE databases were searched for publications from 1966 to 2009 relating to intracranial hemorrhage and antiplatelet agents. The reference sections of recent articles, guidelines and reviews were reviewed and pertinent articles identified. Studies were classified by two broad subsets; those describing intracranial hemorrhage relatable to a traumatic mechanism and those with a spontaneous intracranial hemorrhage. Two independent auditors recorded and analyzed study design and the reported outcome measures.

Results: For the spontaneous intracranial hemorrhage group, 9 reports assessing antiplatelet effects on various outcome measures were identified. Eleven studies evaluating the use of prehospital antiplatlets prior to a traumatic intracranial hemorrhage were examined.

Conclusion: The data assessing the relationship between outcome and prehospital antiplatelet agents in the setting of ICH is conflicting in both the trauma and the stroke literature. Only one retrospective review specifically addressed outcomes after attempted reversal with platelet transfusion. Further study is needed to determine whether platelet transfusion ameliorates hematoma enlargement and/or improves outcome in the setting of acute ICH.

Objective: Presently, equipment available for spinal cord stimulation is adapted for insertion into the subcutaneous space over the occipital nerves. Many technical factors need to be reassessed to optimize the therapy.

Methods: We performed a retrospective review of patients implanted from 2003 to 2007 at a single center. We aimed to analyze the rate of surgical complications related to implantation technique. A total of 28 patients were present for analysis. Patients were followed up to 60 months with a mean follow-up of 21 months.

Results: There is a 32% revision rate for electrode migration or displacement, 3.6% removal rate for infection, and a 21% removal rate for lack of efficacy. Although not well studied secondary to small patient populations, this was consistent with a review of the literature which demonstrated a 10-60% revision rate. Other factors such as anchoring strategy, strain relief, and battery location were all considered in the analysis and will be presented. A major determination was that use of a second incision with an additional strain relief loop had only a 10% revision rate of the lead while those without this additional strain relief loop had a 62.5% revision rate.

Conclusion: Many technical factors need to be addressed for optimization of occipital nerve stimulation.

Objectives: To define the variability of neurologic examination and recovery after non-penetrating complete thoracic spinal cord injuries (ASIA A).

Background Data: Neurologic examinations after SCI can be difficult and inconsistent. Unlike cervical SCI patients, alterations in thoracic (below T1) complete SCI (ASIA A – based on the ASIA Impairment Scale [AIS]) patients’ exams are based only on sensory testing, thus changes in the neurological level (NL) are determined only by sensory changes.

Methods: A retrospective review of the placebo control patients in a multicenter prospective database utilized for the pharmacologic trial of Sygen. Patients were included if they had a complete thoracic SCI on initial evaluation, with completed ASIA examinations at follow-up weeks 4, 8, 16, 26 and 52. Specifically, pin prick (PP) and light touch (LT) were assessed and the absolute change was calculated as the number of spinal levels at a given observation time. Results 3165 patients were initially screened for the Sygen clinical trial, of which 57 were the control placebo patients used in this analysis. Alterations from the baseline exam (PP and LT) were fairly consistent and the median change/recovery in neurologic examination was one spinal level. Across all observations post-baseline, the average change for PP was 1.48 +/- 0.13 (mean +/- SE), and for LT, 1.40 +/-0.13. There were equal proportions of directional changes (none, improved, lost).

Conclusions: Changes in a thoracic complete (ASIA A) SCI patient ASIA examination as measured through sensory modalities (PP/LT) are fairly uncommon. The overall examination had only 1-2 level variability across patients, indicating minimal change in the sensory exam over the follow-up period. Stability in the ASIA examination as measured through sensory modalities has thus been demonstrated over time, making it an excellent tool to monitor changes in neurologic function.