Reversibility of white matter changes and dementia after treatment of dural fistulas.

We describe two patients with dural fistulas who presented with dementia and diffuse white matter signal changes on MR that significantly improved after surgery. One patient had preoperative embolization.     

The fate of buried vaginal epithelium.

A new technique in the treatment of stress urinary incontinence utilizes a sling fashioned from a rectangular island of buried vaginal epithelium. We developed a model to study the natural history of vaginal wall covered by an epithelial flap in 12 rabbits sacrificed at intervals to 26 weeks. Histopathologic examination demonstrated an immediate acute inflammatory reaction. This early response was followed by formation of an epithelial lining of the potential space overlying the buried vaginal tissue. Acute inflammatory cells continued to enter this lumen until week 20, when granulomas were first detected. Histopathologic examination at twenty-six weeks showed stratified squamous epithelium lining the lumen. No deleterious inflammatory sequelae were detected, and no dysplastic or malignant changes were identified. These results suggest that buried vaginal epithelium is a safe (short term) tissue alternative for sling creation.     

Clinical and pathological analysis of spinal cord astrocytomas in children

Twelve children with pathologically confirmed, well-differentiated spinal cord astrocytomas were studied, and correlations among the degree of resection, pathological characteristics, and time of recurrence were examined. Eight tumors were sampled for biopsy or subtotally resected, and 4 were thought to have been totally removed. Clinical recurrence was seen in 4 of 12 patients, 2 of whom died of their disease. The time to recurrence was 1, 2, 2, and 35 years, respectively. The other 8 children remain free of symptoms, with follow-up ranging from 6 months to 35 years (mean, 8.8 years). In 3 of 8 patients who underwent biopsy or subtotal resection, the tumor recurred, and 2 patients died, whereas there was one recurrence in the patients in whom a "total" resection had been obtained. The histologically well-differentiated nature of the lesions correlated well with the relatively prolonged clinical course seen in this series during the period of observation. The relatively long clinical courses seen in our limited series should be considered before high-risk therapy for spinal cord astrocytomas in children is implemented. The presence of four pilocytic astrocytomas in this group was of special interest, and it seems likely that these discrete neoplasms can be distinguished from the more infiltrating fibrillary astrocytic neoplasms by magnetic resonance imaging with enhancement with gadopentetate dimeglumine.     

A critical appraisal of the reporting of the National Acute Spinal Cord Injury Studies (II and III) of methylprednisolone in acute spinal cord injury

From the beginning, the reporting of the results of National Acute Spinal Cord Injury Studies (NASCIS) II and III has been incomplete, leaving clinicians in the spinal cord injury (SCI) community to use or avoid using methylprednisolone in acute SCI on the basis of faith rather than a publicly developed scientific consensus. NASCIS II was initially reported by National Institutes of Health announcements, National Institutes of Health facsimiles to emergency room physicians, and the news media. The subsequent report in the New England Journal of Medicine implied that there was a positive result in the primary efficacy analysis for the entire 487 patient sample. However, this analysis was in fact negative, and the positive result was found only in a secondary analysis of the subgroup of patients who received treatment within 8 hours. In addition, that subgroup apparently had only 62 patients taking methylprednisolone and 67 receiving placebo. The NASCIS II and III reports embody specific choices of statistical methods that have strongly shaped the reporting of results but have not been adequately challenged or or even explained. These studies show statistical artifacts that call their results into question. In NASCIS II, the placebo group treated before 8 hours did poorly, not only when compared with the methylprednisolone group treated before 8 hours but even when compared with the placebo group treated after 8 hours. Thus, the positive result may have been caused by a weakness in the control group rather than any strength of methylprednisolone. In NASCIS III, a randomization imbalance occurred that allocated a disproportionate number of patients with no motor deficit (and therefore no chance for recovery) to the lower dose control group. When this imbalance is controlled for, much of the superiority of the higher dose group seems to disappear. The NASCIS group's decision to admit persons with minor SCIs with minimal or no motor deficit not only enables statistical artifacts it complicates the interpretation of results from the population actually sampled. Perhaps one half of the NASCIS III sample may have had at most a minor deficit. Thus, we do not know whether the results of these studies reflect the severely injured population to which they have been applied. The numbers, tables, and figures in the published reports are scant and are inconsistently defined, making it impossible even for professional statisticians to duplicate the analyses, to guess the effect of changes in assumptions, or to supply the missing parts of the picture. Nonetheless, even 9 years after NASCIS II, the primary data have not been made public. The reporting of the NASCIS studies has fallen far short of the guidelines of the ICH/FDA and of the Evidence-based Medicine Group. Despite the lucrative "off label" markets for methylprednisolone in SCI, no Food and Drug Association indication has been obtained. There has been no public process of validation. These shortcomings have denied physicians the chance to use confidently a drug that many were enthusiastic about and has left them in an intolerably ambiguous position in their therapeutic choices, in their legal exposure, and in their ability to perform further research to help their patients.     

Erythropoietin has an anti-myeloma effect - a hypothesis based on a clinical observation supported by animal studies

Recombinant human erythropoietin (rHuEpo) was introduced into clinical practice more than a decade ago, and has been found to be effective in the treatment of several types of anemia, including anemia of end-stage renal failure and cancer-related anemia. No study has suggested that Epo might have an effect on the biology of the disease, nor any survival advantage to cancer patients treated with Epo for anemia has been reported. Here we report six patients with advanced multiple myeloma (MM) with very poor prognostic features, whose expected survival was <6 months. All six patients were treated with rHuEpo for their anemia, either without any chemotherapy or very mild chemotherapy for a short time. Yet, surprisingly they lived for 45-133 months totally from MM diagnosis and 38-94 months with rHuEpo (with a good quality of life). In fact, one patient, is still alive and well, more than 8 yr after chemotherapy was discontinued because of a resistant aggressive disease. The course in these six MM patients led us to hypothesize that Epo might have an antineoplastic or antimyeloma effect. We proceeded and tested that hypothesis in mouse models of myeloma (Mittelman M et al., Proc Natl Acad Sci USA 98:5181,2001). In these models we confirmed that rHuEpo induced tumor regression in about 50% of the BALB/c mice inoculated with MOPC-315 myeloma cells. We then presented evidence that the mechanism is a new immune-mediated phenomenon, via activation of CD8+ T cells. Furthermore, evidence from the literature supports the antineoplastic effect of Epo. Epo might be used as an adjunct immune treatment in various malignant diseases, in addition to the current regimens and chemotherapeutic protocols. Future trials should determine the role of Epo in myeloma and cancer treatment, besides clarifying concerns about the presence of Epo receptors on some tumor cells.     

Segmental stability and compressive strength of posterior lumbar interbody fusion implants

STUDY DESIGN: Human cadaveric study on initial segmental stability and compressive strength of posterior lumbar interbody fusion implants. OBJECTIVES: To compare the initial segmental stability and compressive strength of a posterior lumbar interbody fusion construct using a new cortical bone spacer machined from allograft to that of titanium threaded and nonthreaded posterior lumbar interbody fusion cages, tested as stand-alone and with supplemental pedicle screw fixation. SUMMARY OF BACKGROUND DATA: Cages were introduced to overcome the limitations of conventional allografts. Radiodense cage materials impede radiographic assessment of the fusion, however, and may cause stress shielding of the graft. METHODS: Multisegmental specimens were tested intact, with posterior lumbar interbody fusion implants inserted into the L4/L5 interbody space and with supplemental pedicle screw fixation. Three posterior lumbar interbody fusion implant constructs (Ray Threaded Fusion Cage, Contact Fusion Cage, and PLIF Allograft Spacer) were tested nondestructively in axial rotation, flexion-extension, and lateral bending. The implant-specimen constructs then were isolated and compressed to failure. Changes in the neutral zone, range of motion, yield strength, and ultimate compressive strength were analyzed. RESULTS: None of the stand-alone implant constructs reduced the neutral zone. Supplemental pedicle screw fixation decreased the neutral zone in flexion-extension and lateral bending. Stand-alone implant constructs decreased the range of motion in flexion and lateral bending. Differences in the range of motion between stand-alone cage constructs were found in flexion and extension (marginally significant). Supplemental posterior fixation further decreased the range of motion in all loading directions with no differences between implant constructs. The Contact Fusion Cage and PLIF Allograft Spacer constructs had a higher ultimate compressive strength than the Ray Threaded Fusion Cage. CONCLUSIONS: The biomechanical data did not suggest any implant construct to behave superiorly either as a stand-alone or with supplemental posterior fixation. The PLIF Allograph Spacer is biomechanically equivalent to titanium cages but is devoid of the deficiencies associated with other cage technologies. Therefore, the PLIF Allograft Spacer is a valid alternative to conventional cages.     

PRIMARY CARE FOR WOMEN: Comprehensive Assessment of the Neurologic System

This article reviews the essential neuroanatomy and neurophysiology, and summarizes the components of the health history, physical exam, and laboratory tests required for an assessment of the neurologic system within the primary care setting. Brief case studies illustrate the wide range of symptoms associated with neurologic disorders in women and the manner in which the pattern of symptoms can be used to locate the site of pathology and indicate the need for referral and follow-up.