Alison Wichman

Sarcoma Arising from a Gliosarcoma

An 18-year-old woman with headaches and visual abnormalities was found upon biopsy to have an occipital gliosarcoma, which was treated with irradiation and chemotherapy for a year. Cells in the gliosarcoma tissue were positive for GFAP. At necropsy, only the sarcoma was evident at the site of original surgical removal. The sarcoma had spread widely along meningeal routes, causing the patients death. The biologic behavior and histologic features of the sarcoma were clearly malignant. Cells cultured from the biopsy specimen maintained features in common with sarcoma.

Research involving critically ill subjects in emergency circumstances: New regulations, new challenges

Clinical research in emergency circumstances is important because there is great need to improve understanding of illnesses that kill and maim many people. However, our society has decided by law that advances in scientific knowledge must take place in a way that protects the rights and safeguards the welfare of human research subjects. For many years, a fundamental requirement for research participation has been informed consent. However, informed consent can rarely be obtained from critically ill subjects, and in emergency circumstances, there may not be time to seek consent from their representatives. Therefore, over the past few years, researchers, institutional review boards (IRBs), regulatory agencies, public interest and professional groups, and others have been discussing when, if ever, it is ethically permissible to conduct emergency research without informed consent. This issue is important to neurologists, neurosurgeons, and their patients, as well as to neurologic professional organizations, because many diseases studied in emergency circumstances involve the nervous system. In October 1996, the US Food and Drug Administration (FDA) issuedl and the Department of Health and Human Services (DHHS) agreed to accept2 a new regulation allowing for a waiver of informed consent by subjects or their representatives to participation in certain emergency research studies. This article provides a brief overview of the new regulation and discusses some current difficulties when conducting research in emergency circumstances.

Collaborative research involving human subjects: a survey of researchers using international single project assurances.

much suffering, and death, for many people throughout the world. The Acquired Immunodeficiency Syndrome, malaria, dysentery, nutritional and vitamin-deficiency disorders, a host of infectious diseases, many public health issues, and the effects on humans of exposure to radiation, are under intense study by teams of multinational researchers. As a result of the expansion of international collaborative clinical research, increased attention is being directed to the protection of human research subjects. This interest has been stimulated, in part, by a general agreement among researchers, ethicists, public policymakers, and others

NeurEx: digitalized neurological examination offers a novel high-resolution disability scale

To develop a sensitive neurological disability scale for broad utilization in clinical practice.

New Multiple Sclerosis Disease Severity Scale Predicts Future Accumulation of Disability

The search for the genetic foundation of multiple sclerosis (MS) severity remains elusive. It is, in fact, controversial whether MS severity is a stable feature that predicts future disability progression. If MS severity is not stable, it is unlikely that genotype decisively determines disability progression. An alternative explanation tested here is that the apparent instability of MS severity is caused by inaccuracies of its current measurement. We applied statistical learning techniques to a 902 patient-years longitudinal cohort of MS patients, divided into training (n = 133) and validation (n = 68) sub-cohorts, to test four hypotheses: (1) there is intra-individual stability in the rate of accumulation of MS-related disability, which is also influenced by extrinsic factors. (2) Previous results from observational studies are negatively affected by the insensitive nature of the Expanded Disability Status Scale (EDSS). The EDSS-based MS Severity Score (MSSS) is further disadvantaged by the inability to reliably measure MS onset and, consequently, disease duration (DD). (3) Replacing EDSS with a sensitive scale, i.e., Combinatorial Weight-Adjusted Disability Score (CombiWISE), and substituting age for DD will significantly improve predictions of future accumulation of disability. (4) Adjusting measured disability for the efficacy of administered therapies and other relevant external features will further strengthen predictions of future MS course. The result is a MS disease severity scale (MS-DSS) derived by conceptual advancements of MSSS and a statistical learning method called gradient boosting machines (GBM). MS-DSS greatly outperforms MSSS and the recently developed Age Related MS Severity Score in predicting future disability progression. In an independent validation cohort, MS-DSS measured at the first clinic visit correlated significantly with subsequent therapy-adjusted progression slopes (r = 0.5448, p = 1.56e−06) measured by CombiWISE. To facilitate widespread use of MS-DSS, we developed a free, interactive web application that calculates all aspects of MS-DSS and its contributing scales from user-provided raw data. MS-DSS represents a much-needed tool for genotype-phenotype correlations, for identifying biological processes that underlie MS progression, and for aiding therapeutic decisions.

Identifying and Quantifying Neurological Disability via Smartphone

Embedded sensors of the smartphones offer opportunities for granular, patient-autonomous measurements of neurological dysfunctions for disease identification, management, and for drug development. We hypothesized that aggregating data from two simple smartphone tests of fine finger movements with differing contribution of specific neurological domains (i.e., strength & cerebellar functions, vision, and reaction time) will allow establishment of secondary outcomes that reflect domain-specific deficit. This hypothesis was tested by assessing correlations of smartphone-derived outcomes with relevant parts of neurological examination in multiple sclerosis (MS) patients. We developed MS test suite on Android platform, consisting of several simple functional tests. This paper compares cross-sectional and longitudinal performance of Finger tapping and Balloon popping tests by 76 MS patients and 19 healthy volunteers (HV). The primary outcomes of smartphone tests, the average number of taps (per two 10-s intervals) and the average number of pops (per two 26-s intervals) differentiated MS from HV with similar power to traditional, investigator-administered test of fine finger movements, 9-hole peg test (9HPT). Additionally, the secondary outcomes identified patients with predominant cerebellar dysfunction, motor fatigue and poor eye-hand coordination and/or reaction time, as evidenced by significant correlations between these derived outcomes and relevant parts of neurological examination. The intra-individual variance in longitudinal sampling was low. In the time necessary for performing 9HPT, smartphone tests provide much richer and reliable measurements of several distinct neurological functions. These data suggest that combing more creatively-construed smartphone apps may one day recreate the entire neurological examination.

Chapter 5 – Institutional Review Boards

Publisher Summary This chapter focuses on the development of federal US regulations concerning research involving human subjects and the roles and responsibilities of Institutional Review Boards (IRBs). The research goals include the welfare of individual subjects and the gathering of scientific data for application in the future. Therefore, the society has granted a conditional privilege to perform research with human subjects; the condition is that the research must be scientifically sound and conducted in a manner that protects the rights and safeguards the welfare of the participants. The current US system for protecting human research subjects, including the role of IRBs, is undergoing serious evaluation. The IRB system is well developed but ever evolving. Successful evolution of the system depends on learning from the past, understanding current and future needs, and applying knowledge to implement meaningful improvements.