Zarina S. Ali

ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration.

We report here that amyotrophic lateral sclerosis–linked superoxide dismutase 1 (SOD1) mutants with different biochemical characteristics disrupted the blood–spinal cord barrier in mice by reducing the levels of the tight junction proteins ZO-1, occludin and claudin-5 between endothelial cells. This resulted in microhemorrhages with release of neurotoxic hemoglobin-derived products, reductions in microcirculation and hypoperfusion. SOD1 mutant–mediated endothelial damage accumulated before motor neuron degeneration and the neurovascular inflammatory response occurred, indicating that it was a central contributor to disease initiation.

A comparative morphologic analysis of adult onset leukodystrophy with neuroaxonal spheroids and pigmented glia--a role for oxidative damage.

We performed a blinded study on 5 cases of hereditary diffuse leukoencephalopathy with spheroids and 10 cases of the pigmentary type of orthochromatic leukodystrophy, 6 of the latter having a family history of neurologic illness. Patients presented in the third to sixth decade with behavioral, cognitive, and motor symptoms. All cases displayed widespread myelin loss, predominantly frontotemporal with relative sparing of subcortical U-fibers, and variable numbers of both neuroaxonal spheroids and pigmented glia. Immunohistochemically, spheroids contained amyloid precursor/neurofilament proteins, several neurotransmitters or neuropeptides, and ubiquitin. Cytoplasmic inclusions in glia and numerous pigmented macrophages were autofluorescent and stained consistently with diastase-periodic acid-Schiff, prolonged Ziehl-Nielsen, and Sudan black, but the same cells labeled inconsistently for iron or ferritin. Ultrastructurally, the most characteristic autofluorescent glial lipopigments consisted of bosselated masses of granular, electron-dense material. These morphologic features are those of ceroid, an end-product of oxidative damage. Glial immunoreactivity for markers of oxidative stress (hemeoxygenase-1 and superoxide dismutase 2) and damage (4-hydroxynonenal, malondialdehyde, and nitrotyrosine) was noted, particularly in cases with increased iron and ferritin. These data support the hypothesis that the similar clinicopathologic features of hereditary diffuse leukoencephalopathy with spheroids and the pigmentary type of orthochromatic leukodystrophy reflect a common disease due, at least in part, to an oxidative insult.

Automated Tumor Volumetry Using Computer-Aided Image Segmentation

RATIONALE AND OBJECTIVES Accurate segmentation of brain tumors, and quantification of tumor volume, is important for diagnosis, monitoring, and planning therapeutic intervention. Manual segmentation is not widely used because of time constraints. Previous efforts have mainly produced methods that are tailored to a particular type of tumor or acquisition protocol and have mostly failed to produce a method that functions on different tumor types and is robust to changes in scanning parameters, resolution, and image quality, thereby limiting their clinical value. Herein, we present a semiautomatic method for tumor segmentation that is fast, accurate, and robust to a wide variation in image quality and resolution. MATERIALS AND METHODS A semiautomatic segmentation method based on the geodesic distance transform was developed and validated by using it to segment 54 brain tumors. Glioblastomas, meningiomas, and brain metastases were segmented. Qualitative validation was based on physician ratings provided by three clinical experts. Quantitative validation was based on comparing semiautomatic and manual segmentations. RESULTS Tumor segmentations obtained using manual and automatic methods were compared quantitatively using the Dice measure of overlap. Subjective evaluation was performed by having human experts rate the computerized segmentations on a 0-5 rating scale where 5 indicated perfect segmentation. CONCLUSIONS The proposed method addresses a significant, unmet need in the field of neuro-oncology. Specifically, this method enables clinicians to obtain accurate and reproducible tumor volumes without the need for manual segmentation.

Direct versus indirect revascularization procedures for moyamoya disease: a comparative effectiveness study.

OBJECTIVE Moyamoya disease (MMD) is a chronic cerebrovascular disease that can lead to devastating neurological outcomes. Surgical intervention is the definitive treatment, with direct, indirect, and combined revascularization procedures currently employed by surgeons. The optimal surgical approach, however, remains unclear. In this decision analysis, the authors compared the effectiveness of revascularization procedures in both adult and pediatric patients with MMD. METHODS A comprehensive literature search was performed for studies of MMD. Using complication and success rates from the literature, the authors constructed a decision analysis model for treatment using a direct and indirect revascularization technique. Utility values for the various outcomes and complications were extracted from the literature examining preferences in similar clinical conditions. Sensitivity analysis was performed. RESULTS A structured literature search yielded 33 studies involving 4197 cases. Cases were divided into adult and pediatric populations. These were further subdivided into 3 different treatment groups: indirect, direct, and combined revascularization procedures. In the pediatric population at 5- and 10-year follow-up, there was no significant difference between indirect and combination procedures, but both were superior to direct revascularization. In adults at 4-year follow-up, indirect was superior to direct revascularization. CONCLUSIONS In the absence of factors that dictate a specific approach, the present decision analysis suggests that direct revascularization procedures are inferior in terms of quality-adjusted life years in both adults at 4 years and children at 5 and 10 years postoperatively, respectively. These findings were statistically significant (p < 0.001 in all cases), suggesting that indirect and combination procedures may offer optimal results at long-term follow-up.

Ultrasonographic Evaluation of Peripheral Nerves

There are a variety of imaging modalities for evaluation of peripheral nerves. Of these, ultrasonography (US) is often underused. There are several advantages of this imaging modality, including its cost-effectiveness, time-efficient assessment of long segments of peripheral nerves, ability to perform dynamic maneuvers, lack of contraindications, portability, and noninvasiveness. It can provide diagnostic information that cannot be obtained by electrophysiologic or, in some cases, magnetic resonance imaging studies. Ideally, the neurosurgeon can use US as a diagnostic adjunct in the preoperative assessment of a patient with traumatic, neoplastic, infective, or compressive nerve injury. Perhaps its most unique use is in intraoperative surgical planning. In this article, a brief description of normal US nerve anatomy is presented followed by a description of the US appearance of peripheral nerve disease caused by trauma, tumor, infection, and entrapment.

Predictive value of 3-month lumbar discectomy outcomes in the NeuroPoint-SD Registry

OBJECT The authors have established a multicenter registry to assess the efficacy and costs of common lumbar spinal procedures using prospectively collected outcomes. Collection of these data requires an extensive commitment of resources from each site. The aim of this study was to determine whether outcomes data from shorter-interval follow-up could be used to accurately estimate long-term outcome following lumbar discectomy. METHODS An observational prospective cohort study was completed at 13 academic and community sites. Patients undergoing single-level lumbar discectomy for treatment of disc herniation were included. SF-36 and Oswestry Disability Index (ODI) data were obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. Quality-adjusted life year (QALY) data were calculated using SF-6D utility scores. Correlations among outcomes at each follow-up time point were tested using the Spearman rank correlation test. RESULTS One hundred forty-eight patients were enrolled over 1 year. Their mean age was 46 years (49% female). Eleven patients (7.4%) required a reoperation by 1 year postoperatively. The overall 1-year follow-up rate was 80.4%. Lumbar discectomy was associated with significant improvements in ODI and SF-36 scores (p < 0.0001) and with a gain of 0.246 QALYs over the 1-year study period. The greatest gain occurred between baseline and 3-month follow-up and was significantly greater than improvements obtained between 3 and 6 months or 6 months and 1 year(p < 0.001). Correlations between 3-month, 6-month, and 1-year outcomes were similar, suggesting that 3-month data may be used to accurately estimate 1-year outcomes for patients who do not require a reoperation. Patients who underwent reoperation had worse outcomes scores and nonsignificant correlations at all time points. CONCLUSIONS This national spine registry demonstrated successful collection of high-quality outcomes data for spinal procedures in actual practice. Three-month outcome data may be used to accurately estimate outcome at future time points and may lower costs associated with registry data collection. This registry effort provides a practical foundation for the acquisition of outcome data following lumbar discectomy.

Conservative Management of Presumed Low-Grade Gliomas in the Asymptomatic Pediatric Population

OBJECTIVE The optimal management of asymptomatic children with small, nonenhancing intracranial lesions presumed to be low-grade gliomas (LGGs) is not entirely clear in the literature. However, surgical intervention via resection or biopsy is not without risk and is of questionable long-term benefit in children with stable lesions. We present a series of 12 patients with incidentally detected, small, nonenhancing, intracranial lesions that were managed with watchful waiting and serial magnetic resonance imaging (MRI) scans. METHODS We retrospectively reviewed a series of 12 children (eight boys, four girls) with T1 hypointense and T2 hyperintense intracranial lesions <2 cm without enhancement or surrounding edema. RESULTS Most patients (n = 5, 41.7%) received MRI studies after suffering a traumatic injury with evidence of an abnormality seen on computed tomography scan. Others received MRI scan as part of headache work-up (n = 4, 33.3%). The majority of lesions were located infratentorially (n = 8, 66.7%), whereas other locations included the frontal lobe and thalamus. The median age of the patients upon identification of the intracranial abnormality was 10 years (range, 1-19 years of age). Patients were followed for a median of 16.7 months (range, 2.7-59.5 months). The most common diagnosis based on clinical and radiographic features of these lesions consisted of LGG. No patient underwent surgery, radiation therapy, or chemotherapy except one patient, in whom the lesion grew in size. Surgical pathologic diagnosis in this case confirmed World Health Organization grade II astrocytoma. CONCLUSIONS Our case series suggests that conservative management and close follow-up of incidental radiographic lesions consistent with LGGs is a safe and effective initial strategy in the pediatric population. In cases in which lesion size or quality changes, surgical resection may be necessary to confirm diagnosis. Further studies that include a larger number of patients and longer follow-up period are required to compare outcomes between this approach and initial surgical, radiation, or chemotherapy management strategies.

Patient choice of provider type in the emergency department: perceptions and factors relating to accommodation of requests for care providers

Background Patient satisfaction is related to the perception of care. Some patients prefer, and are more satisfied with, providers of the same gender, race or religious faith. This study examined emergency medical provider attitudes towards, as well as patient and provider characteristics that are associated with, accommodating such requests. Methods A survey administered to a convenience sample of participants at the 2007 American College of Emergency Physicians Scientific Assembly. The nine-question survey ascertained Likert-type responses to the likelihood of accommodating patient requests for specific provider types. Statistical analyses used Wilcoxon rank-sum, Wilcoxon signed-rank and Cochrans Q tests. Results The 176 respondents were predominately white (83%) and male (74%), with a mean age of 42 y. Nearly a third of providers felt that patients perceive better care from providers of shared demographics with racial matching perceived as more important than gender or religion (p=0.02). Female providers supported patient requests for same gender providers more so than males (p<0.01). Provider race, practice location, type and duration did not significantly affect the level of accommodation. When requesting like providers, female patients had higher accommodation scores than male patients (p<0.001), non-whites than whites (p<0.05), with Muslim patients (male or female) most likely to be accommodated (p<0.01). Conclusion Accommodating patient requests for providers of specific demographics within the emergency department may be related to provider characteristics. When patients ask for same gender providers, female providers are more likely to accommodate such a request than male providers. Female, non-white and Muslim patients may be more likely to have their requests honoured for matched providers.

Pre-optimization of spinal surgery patients: Development of a neurosurgical enhanced recovery after surgery (ERAS) protocol

OBJECTIVE Despite surgical, technological, medical, and anesthetic improvements, patient outcomes following elective neurosurgical procedures can be associated with high morbidity. Enhanced recovery after surgery (ERAS) protocols are multimodal care pathways designed to optimize patient outcomes by addressing pre-, peri-, and post-operative factors. Despite significant data suggesting improved patient outcomes with the adoption of these pathways, development and implementation has been limited in the neurosurgical population. METHODS/RESULTS This study protocol was designed to establish the feasibility of a randomized controlled trial to assess the efficacy of implementation of an ERAS protocol on the improvement of clinical and patient reported outcomes and patient satisfaction scores in an elective inpatient spine surgery population. Neurosurgical patients undergoing spinal surgery will be recruited and randomly allocated to one of two treatment arms: ERAS protocol (experimental group) or hospital standard (control group). The experimental group will undergo interventions at the pre-, peri-, and post-operative time points, which are exclusive to this group as compared to the hospital standard group. CONCLUSIONS The present proposal aims to provide supporting data for the application of these specific ERAS components in the spine surgery population and provide rationale/justification of this type of care pathway. This study will help inform the design of a future multi-institutional, randomized controlled trial. RESULTS of this study will guide further efforts to limit post-operative morbidity in patients undergoing elective spinal surgery and to highlight the impact of ERAS care pathways in improving patient reported outcomes and satisfaction.

Ultrasonography Detects Ulnar Nerve Dislocation Despite Normal Electrophysiology and Magnetic Resonance Imaging

BACKGROUND Dislocation of the ulnar nerve (UN) occurs in a subset of patients with ulnar neuropathy. Electrodiagnostic and magnetic resonance imaging (MRI) studies are performed to support the clinical diagnosis. We report the case of a patient with ulnar neuropathy with normal electrodiagnostic and MRI studies but with ultrasonography (US) showing UN dislocation, which prompted successful treatment by UN submuscular transposition. CASE DESCRIPTION A healthy 15-year-old female softball player presented with right medial elbow pain and paresthesias of the fourth and fifth digits. She had 4+/5 strength in the right hand intrinsic muscles and a Tinel sign at the right elbow. A snap was palpated at the elbow upon flexion. MRI showed mild common flexor tendonitis, and electrodiagnostic studies showed normal motor responses and no conduction block at the elbow. High-resolution US showed dislocation of the UN over the medial epicondyle. UN dislocation was confirmed intraoperatively, and, after UN submuscular transposition, the patient reported complete resolution of her preoperative symptoms at 6-week follow-up and continued resolution at 1 year. CONCLUSIONS Normal findings on electrodiagnostic or MRI studies should not immediately dissuade surgeons from operating on a symptomatic patient with a clinical examination supporting ulnar neuropathy and with US evidence of UN dislocation, because such a patient may experience postoperative symptom relief. Furthermore, the dynamic capability of US imaging complements data obtained from electrodiagnostic and MRI studies, especially when these tests are normal, and it should be considered by clinicians when evaluating patients with medial elbow pain or signs of ulnar neuropathy.