Laboratory Study Slope analysis of somatosensory evoked potentials in spinal cord injury for detecting contusion injury and focal demyelination Gracee Agrawal a , David Sherman b , Anil Maybhate a, * , Michael Gorelik c , Douglas A. Kerr c , Nitish V. Thakor a , Angelo H. All a,c a Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Traylor 710B, Baltimore, Maryland 21205, USA b Infinite Biomedical Technologies LLC, 3600 Clipper Mill Rd, Suite 410, Baltimore, Maryland 21211, USA c Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA article info Article history: Received 7 February 2010 Accepted 17 February 2010 Available online xxxx Keywords: Contusion Experimental autoimmune encephalomyelitis Rat model Somatosensory evoked potentials Spinal cord injury abstract In spinal cord injury (SCI) research there is a need for reliable measures to determine the extent of injury and assess progress due to natural recovery, drug therapy, surgical intervention or rehabilitation. Somatosensory evoked potentials (SEP) can be used to quantitatively examine the functionality of the ascending sensory pathways in the spinal cord. A reduction of more than 50% in peak amplitude or an increase of more than 10% in latency are threshold indicators of injury. However, in the context of injury, SEP peaks are often obscured by noise. We have developed a new technique to investigate the morphol- ogy of the SEP waveform, rather than focusing on a small number of peaks. In this study, we compare SEP signals before and after SCI using two rat models: a contusion injury model and a focal experimental autoimmune encephalomyelitis model. Based on mean slope changes over the signal, we were able to effectively differentiate pre-injury and post-injury SEP values with high levels of sensitivity (83.3%) and specificity (79.2%). Ó 2010 Elsevier Ltd. All rights reserved. 1. Introduction Based on an average annual incidence of approximately 40 cases per million people in the United States, it is estimated that more than 12 000 people survive a spinal cord injury (SCI) each year. 1 Around 258 000 people in the United States are reportedly living with the devastating effects of an SCI. 1 On the basis of etiol- ogy, there are two general types of SCI: traumatic (due to blunt mechanical impact) and non-traumatic (due to vascular, ischemic or neoplastic causes, or immunological disorders). Traumatic SCI accounts for nearly 60% of all injuries to the spinal cord. 2 The number of spared axonal fibers and the degree to which they are demyelinated play important roles in determining the residual functionality present after SCI. ‘‘Anatomically incomplete” injuries are those in which a number of spared but demyelinated axons remain intact across the lesion, without electrophysiological re- sponses. 3–6 Even a small number of spared fibers remaining after SCI can greatly improve the quality of life of SCI patients. Develop- ment of therapeutic strategies to reduce secondary injury, and to remyelinate spared, demyelinated axons has generated considerable interest in the past. 7–9 When evaluating any therapeutic approach for SCI, a suitable SCI animal model and reliable monitoring measures are essential, to allow calibration of the severity of the SCI and monitor- ing of the progress of injury and extent of recovery. 10,11 A popular animal model of SCI for blunt contusion injuries is a rat model with injury induced using the New York University (NYU) impactor, 12 which is known to reliably emulate the patho- physiology seen in humans after SCI. 13 In this model, some neuro- nal tissue remains intact along the periphery of the primary site of injury, 13 similar to the situation in humans after blunt injury. 3 A chemically mediated SCI model is a targeted approach to sim- ulate specific aspects of SCI-like demyelination, inflammation, ischemia or immunological disorders. 14 A focal demyelinating lesion can be induced in the spinal cord of the rat experimental autoimmune encephalomyelitis (EAE) model by administering inflammatory factors directly into the spinal cord of the immu- nized rat. 15 This model is analogous to the human paralyzing disorder transverse myelitis, which often arises idiopathically or in association with multiple sclerosis. Various outcome measures for animal models can be used to as- sess changes due to endogenous recovery, drug therapy, surgical intervention or rehabilitation. Behavioral tests can be used to examine functional recovery in laboratory animals after SCI; how- ever, such tests are often subjective. In contrast, electrophysiolog- ical techniques present an objective means for quantitative, non- invasive, accurate assessment of the integrity of neural pathways. Somatosensory evoked potential (SEP) is the electrophysiological 0967-5868/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2010.02.005 * Corresponding author. Tel.: +1 443 287 6341; fax: +1 410 502 9814. E-mail address: anil@jhmi.edu (A. Maybhate). Journal of Clinical Neuroscience xxx (2010) xxx–xxx Contents lists available at ScienceDirect Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn Please cite this article in press as: Agrawal G et al. Slope analysis of somatosensory evoked potentials in spinal cord injury for detecting contusion injury and focal demyelination. J Clin Neurosci (2010), doi:10.1016/j.jocn.2010.02.005