Name: a neuroscientific approach to the examination of concussions in student-athletes
Uploaded: 2014-12-08T14:00:00
Description: Watch this Scientific Journal Video about A Neuroscientific Approach to the Examination of Concussions in Student-Athletes at JoVE.com

This study was supported by grants from the American Medical Society for Sports Medicine. The authors would like to acknowledge and show our appreciation for our undergraduate research students including David Lawton, Drew Gardner, Mark Sundman, Kelsey Evans, Graham Cochrane, Jordan Cottle and Jack Halligan for their assistance in data collection over the past four years.

All the procedures described below have been approved by the Elon&#8217;s Institutional Review Board.
1. Computerized Neurocognitive Testing
<ol>
	<li>Ask the participants to be seated in front of the computer. Log participants on to system and instruct them to complete the computerized neuropsychological test which consists a demographic and background information section, self-reported symptom checklist, and 6 modules (word discrimination, design memory, X&#8217;s and O&#8217;s, symbol mat...

<ol>
	<li>Kristman, V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Does+the+Apolipoprotein+E4+allele+predispose+varsity+athletes+to+concussion?+A+prospective+cohort+study.">Does the Apolipoprotein E4 allele predispose varsity athletes to concussion? A prospective cohort study.</a> Clin J Sports Med. 18, 322-328 (2008).</li><li>McCrory, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Consensus+statement+on+concussion+in+sports+the+4th+International+Conference+on+Concussion+held+in+Zurich,+November+2012.">Consensus statement on concussion in sports the 4th International Conference on Concussion held in Zurich, November 2012.</a> Br J Sports Med. 47 (5), 250-258 (2012).</li><li>Giza, C. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Summary+of+evidence-based+guideline+update:+Evaluation+and+management+of+concussion+in+sports:+Report+of+the+Guideline+Development+Subcommittee+of+the+American+Academy+of+Neurology.">Summary of evidence-based guideline update: Evaluation and management of concussion in sports: Report of the Guideline Development Subcommittee of the American Academy of Neurology.</a> Neurology. 80 (24), 2250-2257 (2013).</li><li>Langlois, J. A., Rutland-Brown, W., Waid, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+epidemiology+and+impact+of+traumatic+brain+injury:+a+brief+overview.">The epidemiology and impact of traumatic brain injury: a brief overview.</a> J Head Trauma Rehabil. 21, 375-378 (2006).</li><li>Faul, M., Xu, L., Wald, M. M., Coronado, V. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Traumatic+brain+injury+in+the+United+States:+emergency+department+visits,+hospitalizations,+and+deaths.">Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths.</a> Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. , (2010).</li><li>Broglio, S. P., Puetz, T. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effect+of+sport+concussion+on+neurocognitive+function,+self-report+symptoms+and+postural+control:+a+meta-analysis.">The effect of sport concussion on neurocognitive function, self-report symptoms and postural control: a meta-analysis.</a> J Sports Med. 38, 53-67 (2008).</li><li>Cancelliere, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Protocol+for+a+systematic+review+of+prognosis+after+mild+traumatic+brain+injury:+an+update+of+the+WHO+Collaborating+Centre+Task+Force+findings.">Protocol for a systematic review of prognosis after mild traumatic brain injury: an update of the WHO Collaborating Centre Task Force findings.</a> Systematic Reviews. 1, 17 .</li><li>Guskiewicz, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cumulative+effects+associated+with+recurrent+concussion+in+collegiate+football+players.">Cumulative effects associated with recurrent concussion in collegiate football players.</a> JAMA. 290, 2549-2555 (2003).</li><li>Makdissi, M., Darby, D., Maruff, P., Ugoni, A., Brukner, P., McCrory, P. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Natural+history+of+concussions+in+sport:+markers+of+severity+and+implications+for+management.">Natural history of concussions in sport: markers of severity and implications for management.</a> Am J Sports Med. 38, 464-471 .</li><li>Kirkwood, M. W., Yeates, K. O., Wilson, P. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pediatric+sport-related+concussion:+a+review+of+the+clinical+management+of+an+oft-neglected+population.">Pediatric sport-related concussion: a review of the clinical management of an oft-neglected population.</a> Pediatrics. 117, 1359-1371 (2006).</li><li>McCrea, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acute+effects+and+recovery+time+following+concussion+in+collegiate+football+players.">Acute effects and recovery time following concussion in collegiate football players.</a> the NCAA Concussion Study. JAMA. 290, 2556-2563 (2003).</li><li>Henry, L. C., Tremblay, S., Boulanger, Y., Ellemberg, D., Lassonde, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neurometabolic+changes+in+acute+phase+concussions+correlate+with+symptom+severity.">Neurometabolic changes in acute phase concussions correlate with symptom severity.</a> J Neurotrauma. 27, 65-76 (2010).</li><li>Terrell, T. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=APOE+promotor,+and+Tau+genotypes+and+risk+for+concussion+in+college+athletes.">APOE promotor, and Tau genotypes and risk for concussion in college athletes.</a> Clin J Sports Med. 18, 10-17 (2008).</li><li>Tierney, R. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Apolipoprotein+E+genotype+and+concussion+in+college+athletes.">Apolipoprotein E genotype and concussion in college athletes.</a> Clin J Sports Med. 20, 464-468 (2010).</li><li>Iverson, G., Brooks, B., Collins, M., Lovell, M. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tracking+neuropsychological+recovery+following+concussion+in+sport.">Tracking neuropsychological recovery following concussion in sport.</a> Brain Inj. 20, 245-252 (2006).</li><li>McClincy, M. P., Lovell, M. R., Pardini, J., Collins, M. W., Spore, M. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recovery+from+sports+concussion+in+high+school+and+collegiate+athletes.">Recovery from sports concussion in high school and collegiate athletes.</a> Brain Inj. 20, 33-39 (2006).</li><li>Hootman, J., Dick, R., Agel, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Epidemiology+of+collegiate+injuries+for+15+sports:+summary+and+recomendations+for+injury+prevention+initiatives.">Epidemiology of collegiate injuries for 15 sports: summary and recomendations for injury prevention initiatives.</a> J Athl Train. 43, 311-319 (2007).</li><li>Johnson, E. W., Kegel, N. E., Collins, M. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuropsychological+assessment+of+sport-related+concussion.">Neuropsychological assessment of sport-related concussion.</a> Clin Sports Med. 30 (1), 78-88 (2011).</li><li>Broglio, S. P., Pontifex, M. B., O'Connor, P., Hillman, C. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+persistent+effects+of+concussion+on+neuroelectric+indices+of+attention.">The persistent effects of concussion on neuroelectric indices of attention.</a> J Neurotrauma. 26 (9), 1463-1470 (2009).</li><li>Holden, J. K., Nguyen, R. H., Francisco, E. M., Zhang, Z., Dennis, R. G., Tommerdahl, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+device+for+the+study+of+somatosensory+information+processing.">A novel device for the study of somatosensory information processing.</a> J Neurosci Methods. 204 (2), 215-220 (2011).</li><li>Martini, D. N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+chronic+effects+of+concussion+on+gait.">The chronic effects of concussion on gait.</a> Arch Phys Med Rehabil. 92, 585-589 (2011).</li><li>Jordan, B. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Genetic+influences+on+outcome+following+traumatic+brain+injury.">Genetic influences on outcome following traumatic brain injury.</a> Neurochem Res. 32, 905-915 (2007).</li><li>Holden, J. K., Nguyen, R. H., Francisco, E. M., Zhang, Z., Dennis, R. G., Tommerdahl, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+device+for+the+study+of+somatosensory+information+processing.">A novel device for the study of somatosensory information processing.</a> J Neurosci Methods. 204, 215-220 (2012).</li><li>Tannan, V., Holden, J. K., Zhang, Z., Baranek, G. T., Tommerdahl, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Perceptual+metrics+of+individuals+with+autism+provide+evidence+for+disinhibition.">Perceptual metrics of individuals with autism provide evidence for disinhibition.</a> Autism Res. 1, 223-230 (2008).</li><li>Nelson, A. J., Permiji, A., Rai, N., Hogue, T., Tommerdahl, M., Chen, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dopamine+alters+tactile+perception+in+Parkinson&#8217;s+disease.">Dopamine alters tactile perception in Parkinson&#8217;s disease.</a> Can J Neurol Sci. 39, 52-57 (2012).</li><li>McCrory, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Future+advances+and+areas+of+future+focus+in+the+treatment+of+sport-related+concussion.">Future advances and areas of future focus in the treatment of sport-related concussion.</a> Clin Sports Med. 30, 201-208 (2011).</li></ol>

The goal of this multidimensional approach to baseline concussion testing is twofold: 1) to better understand the impact of a concussion (acute and long term) on the neuromuscular system; 2) to help the sports medicine staff make return to play decisions (they primarily use neurocognitive testing as has been suggested by McCrory).26 This multifaceted approach to concussion evaluation provides valuable information related to the etiology, functional changes, and recovery from concussion. Little is understood ab...

Concussions are occurring at alarming rates in the United States and have garnered quite a lot of attention as a public health concern.1-3 US Centers for Disease Control and Prevention (CDC) estimates that 1.6 to 3.8 million concussions occur in sports and recreational activities annually.4,5 Concussion as defined by the 2013 Concussion Consensus Statement2 &#8220;may be caused either by a direct blow to the head, face, neck or elsewhere on the body with an &#8216;impulsive&#8217; force transmitted to the head.&#8221; Concussion may result in neuropathological and/or substructural changes that may result in functional disturbances.2 These deficits may persist for several weeks. It is not uncommon for athletes to experience increased self-reported symptoms, decrements in postural control, and decreased neurocognitive function even 14 days following the initial injury.6 The prolonged nature of symptoms, the inconsistent identification of concussions, and the variability in preinjury abilities often lead to complex and non standardized return-to-play decisions by physicians, uncertain recovery times, and possibly long-term sequelae.7-9
Following a concussion, an individual may experience both short-term and long-term effects. The short-term effects of sport related concussions may include changes in playing ability, confusion, memory disturbance, the loss of consciousness, slowing of reaction time, loss of coordination, headaches, dizziness, vomiting, changes in sleep patterns and mood changes. These symptoms typically resolve in a matter of days.2,10 However, while some individuals recover from a single concussion rather quickly, many experience lingering effects that can last for weeks or months following the injury.10,11, 12 These symptomatic disturbances to daily function can be quantified using cognitive and performance related tests. While no one single test should determine diagnosis of a concussion, a battery of tests and known relationships between tests can aid the medical staff in making diagnoses, return to classroom, and return to play decisions.2
There is great variability in an individual&#8217;s risk for concussion and their corresponding recovery.11 The factors related to concussion susceptibility and recovery time course are not well known or understood. Several factors have been suggested that may impact an individual&#8217;s concussion susceptibility and recovery. These factors include the individual&#8217;s concussion history, the severity of the initial injury, history of migraines, history of learning disabilities, history of psychiatric comorbidities, and possibly genetic factors.7, 9, 13, 14
Many studies have individually investigated specific factors for both the short-term and long-term effects of concussions, recovery time course, and genetics as a factor of concussions.4,8,15-17 What has not been clearly established is an effective multifaceted approach to concussion evaluation that would yield valuable information related to the etiology, functional changes, and recovery from concussion. Due to the variety of symptoms and the uncertain time course of recovery, a multifaceted approach to concussion evaluation is warranted and this should include baseline testing of all athletes prior to participation in practice and competition as well as timely evaluation post injury. A recent review suggests that neurocognitive assessments may be more sensitive to recovery from a concussion than monitoring symptoms alone.18 It may be that there are other objective measures that may be better indicators of recovery from concussion.
For this protocol, we use several tasks to assess various components of the system to see how they are impacted by a concussion. A computerized neurocognitive test can assess memory, processing speed, problem solving skills, cognitive efficiency and impulse control.6 EEG with auditory and visual processing tasks can be used to assess neuroefficiency through the examination of event related potentials.19 A somatosensory discrimination task can be used to assess peripheral and central sensory processing capabilities.20 Balance and gait measures can be used to assess functional performance capabilities.6,21 In addition, we assess various genotypes that may have relations to concussion history, concussion recovery and cognitive function.22 We baseline test our varsity student-athletes on this battery of tests and repeat tests if they incur a concussion when asymptomatic.
The purpose of this project is to assess potential short-term and long-term decrements in performance as a result of concussions using genetic, neurocognitive, electrophysiological, behavioral, somatosensory, balance and gait measures. Understanding the potential mechanisms that may be related to various symptoms and impairments that occur with a concussion are important in furthering our knowledge about concussion. Greater knowledgle about these changes may in the future aid in concussion diagnosis as well as concussion management as it relates to return to play and return to academics.
All measures described below are taken at baseline (before student-athlete participation in sport). Our current protocol is to complete the computerized neurocognitive testing at 48 hr along with the balance protocol because we believe that these provide useful information regarding recovery and possible return-to-play and return-to-academics. When the student-athlete reports asymptomatic they again return to the laboratory where all baseline measures are again conducted, except for genetic testing. The full protocol, baseline and asymptomatic, takes approximately 90 min to complete in one testing period.

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	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Name of Material/ Equipment</td>
			<td style="width:356px;">Company</td>
			<td style="width:119px;">Catalog Number</td>
			<td style="width:167px;">Comments/Description</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:216px;">ImPACT</td>
			<td style="width:356px;">ImPACT, Pittsburgh, PA</td>
			<td style="width:119px;"></td>
			<td>Neurocognitive concussion testing</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">EEG</td>
			<td style="width:356px;">EGI, Eugene, OR</td>
			<td style="width:119px;"></td>
			<td>EEG 32-channel system</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Stim2</td>
			<td style="width:356px;">Compumedics Neuroscan, Charlotte, NC</td>
			<td style="width:119px;"></td>
			<td>Software for task presentation for flanker task and auditory oddball</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">NetStation</td>
			<td style="width:356px;">EGI, Eugene, OR</td>
			<td style="width:119px;"></td>
			<td>Software for data collection and analysis of EEG</td>
		</tr>
		<tr height="17">
			<td height="17" style="height:17px;width:216px;">Sensory Device</td>
			<td style="width:356px;">Cortical Metrics</td>
			<td style="width:119px;"></td>
			<td>Sensory testing</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Balance System SD</td>
			<td>Biodex Medical Systems, Inc., Shirley, NY</td>
			<td style="width:119px;"></td>
			<td>balance testing</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Force Plate</td>
			<td>AMTI Corp., Watertown, MA, USA</td>
			<td style="width:119px;"></td>
			<td>Gait Initiation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Movement Analysis</td>
			<td>Qualisys AB, Gothenburg, Sweden</td>
			<td style="width:119px;"></td>
			<td>Gait Analysis</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">GAITRite&#160;</td>
			<td style="width:356px;">CIR systems, Inc., Sparta, NJ, USA</td>
			<td style="width:119px;"></td>
			<td>Gait analysis</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:216px;">PCR</td>
			<td style="width:356px;">Applied Biosystems, Foster City, CA</td>
			<td style="width:119px;"></td>
			<td>Genetic Analysis</td>
		</tr>
		<tr height="24">
			<td height="24" style="height:24px;">Matlab</td>
			<td style="width:356px;">Mathworks, Natick, MA, USA</td>
			<td style="width:119px;"></td>
			<td>Gait and balance analysis</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:216px;">Visual 3D</td>
			<td style="width:356px;">C Motion, Inc, Germantown, MD, USA</td>
			<td style="width:119px;"></td>
			<td>3D analysis&#160;</td>
		</tr>
	</tbody>
</table>

a neuroscientific approach to the examination of concussions in student-athletes

Concussions are occurring at alarming rates in the United States and have become a serious public health concern. The CDC estimates that 1.6 to 3.8 million concussions occur in sports and recreational activities annually. Concussion as defined by the 2013 Concussion Consensus Statement &#8220;may be caused either by a direct blow to the head, face, neck or elsewhere on the body with an &#8216;impulsive&#8217; force transmitted to the head.&#8221; Concussions leave the individual with both short- and long-term effects. The short-term effects of sport related concussions may include changes in playing ability, confusion, memory disturbance, the loss of consciousness, slowing of reaction time, loss of coordination, headaches, dizziness, vomiting, changes in sleep patterns and mood changes. These symptoms typically resolve in a matter of days. However, while some individuals recover from a single concussion rather quickly, many experience lingering effects that can last for weeks or months. The factors related to concussion susceptibility and the subsequent recovery times are not well known or understood at this time. Several factors have been suggested and they include the individual&#8217;s concussion history, the severity of the initial injury, history of migraines, history of learning disabilities, history of psychiatric comorbidities, and possibly, genetic factors. Many studies have individually investigated certain factors both the short-term and long-term effects of concussions, recovery time course, susceptibility and recovery. What has not been clearly established is an effective multifaceted approach to concussion evaluation that would yield valuable information related to the etiology, functional changes, and recovery. The purpose of this manuscript is to show one such multifaceted approached which examines concussions using computerized neurocognitive testing, event related potentials, somatosensory perceptual responses, balance assessment, gait assessment and genetic testing.

Computerized Neurocognitive Testing
An example of results for the computerized neurocognitive test can be seen in Figure 1. The computer program elicits composite scores on Verbal Memory, Visual Memory, Visual Motor Speed and Reaction Time which are often used to make return-to-play and return-to-learn concussion management protocols. The verbal and visual memory composites evaluate attentional processes, learning and memory. Visual motor speed measures visual...

Watch this Scientific Journal Video about A Neuroscientific Approach to the Examination of Concussions in Student-Athletes at JoVE.com

A Neuroscientific Approach to the Examination of Concussions in Student-Athletes

There is great variability in an individual&#8217;s risk for concussion and their corresponding recovery. A multifaceted approach to concussion evaluation is warranted; including baseline testing of athletes before participation in sport and timely evaluation post injury. The goal of this protocol is to provide an appropriate multifaceted approach to examine concussions.

Concussions are occurring at alarming rates in the United States and have become a serious public health concern. The CDC estimates that 1.6 to 3.8 ...

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Medicine

Bronchial Thermoplasty:  A Novel Therapeutic Approach to Severe Asthma

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled manner to reduce excessive airway smooth muscle. Reducing airway smooth muscle decreases the ability of the airways to constrict, thereby reducing the frequency of asthma attacks. Bronchial thermoplasty is delivered by the Alair System and is performed in three outpatient procedure visits, each scheduled approximately three weeks apart. The first procedure treats the airways of the right lower lobe, the second treats the airways of the left lower lobe and the third and final procedure treats the airways in both upper lobes. After all three procedures are performed the bronchial thermoplasty treatment is complete.
Bronchial thermoplasty is performed during bronchoscopy with the patient under moderate sedation. All accessible airways distal to the mainstem bronchi between 3 and 10 mm in diameter, with the exception of the right middle lobe, are treated under bronchoscopic visualization. Contiguous and non-overlapping activations of the device are used, moving from distal to proximal along the length of the airway, and systematically from airway to airway as described previously. Although conceptually straightforward, the actual execution of bronchial thermoplasty is quite intricate and procedural duration for the treatment of a single lobe is often substantially longer than encountered during routine bronchoscopy. As such, bronchial thermoplasty should be considered a complex interventional bronchoscopy and is intended for the experienced bronchoscopist. Optimal patient management is critical in any such complex and longer duration bronchoscopic procedure. This article discusses the importance of careful patient selection, patient preparation, patient management, procedure duration, postoperative care and follow-up to ensure that bronchial thermoplasty is performed safely.
Bronchial thermoplasty is expected to complement asthma maintenance medications by providing long-lasting asthma control and improving asthma-related quality of life of patients with severe asthma. In addition, bronchial thermoplasty has been demonstrated to reduce severe exacerbations (asthma attacks) emergency rooms visits for respiratory symptoms, and time lost from work, school and other daily activities due to asthma.

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled manner to reduce excessive airway smooth muscle. Reducing airway smooth muscle decreases the ability of the airways to constrict, thereby reducing the frequency of asthma attacks.

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled ...

The Measurement and Treatment of Suppression in Amblyopia

Amblyopia, a developmental disorder of the visual cortex, is one of the leading causes of visual dysfunction in the working age population. Current estimates put the prevalence of amblyopia at approximately 1-3%1-3, the majority of cases being monocular2. Amblyopia is most frequently caused by ocular misalignment (strabismus), blur induced by unequal refractive error (anisometropia), and in some cases by form deprivation.
Although amblyopia is initially caused by abnormal visual input in infancy, once established, the visual deficit often remains when normal visual input has been restored using surgery and/or refractive correction. This is because amblyopia is the result of abnormal visual cortex development rather than a problem with the amblyopic eye itself4,5 . Amblyopia is characterized by both monocular and binocular deficits6,7 which include impaired visual acuity and poor or absent stereopsis respectively. The visual dysfunction in amblyopia is often associated with a strong suppression of the inputs from the amblyopic eye under binocular viewing conditions8. Recent work has indicated that suppression may play a central role in both the monocular and binocular deficits associated with amblyopia9,10 .
Current clinical tests for suppression tend to verify the presence or absence of suppression rather than giving a quantitative measurement of the degree of suppression. Here we describe a technique for measuring amblyopic suppression with a compact, portable device11,12 . The device consists of a laptop computer connected to a pair of virtual reality goggles. The novelty of the technique lies in the way we present visual stimuli to measure suppression. Stimuli are shown to the amblyopic eye at high contrast while the contrast of the stimuli shown to the non-amblyopic eye are varied. Patients perform a simple signal/noise task that allows for a precise measurement of the strength of excitatory binocular interactions. The contrast offset at which neither eye has a performance advantage is a measure of the "balance point" and is a direct measure of suppression. This technique has been validated psychophysically both in control13,14 and patient6,9,11 populations.
In addition to measuring suppression this technique also forms the basis of a novel form of treatment to decrease suppression over time and improve binocular and often monocular function in adult patients with amblyopia12,15,16 . This new treatment approach can be deployed either on the goggle system described above or on a specially modified iPod touch device15.

Amblyopia is a developmental disorder of the visual cortex that is often accompanied by strong suppression of one eye. We present a new technique for measuring and treating interocular suppression in patients with amblyopia that can be deployed using virtual reality goggles or a portable iPod Touch device.

Amblyopia, a developmental disorder of the visual cortex, is one of the leading causes of visual dysfunction in the working age population. Current ...

Clinical Examination Protocol to Detect Atypical and Classical Scrapie in Sheep

The diagnosis of scrapie, a transmissible spongiform encephalopathy (TSEs) of sheep and goats, is currently based on the detection of disease-associated prion protein by post mortem tests. Unless a random sample of the sheep or goat population is actively monitored for scrapie, identification of scrapie cases relies on the reporting of clinical suspects, which is dependent on the individual&#39;s familiarization with the disease and ability to recognize clinical signs associated with scrapie. Scrapie may not be considered in the differential diagnosis of neurological diseases in small ruminants, particularly in countries with low scrapie prevalence, or not recognized&#160;if it presents as nonpruritic form like atypical scrapie. To aid in the identification of clinical suspects, a short examination protocol is presented to assess the display of specific clinical signs associated with pruritic and nonpruritic forms of TSEs in sheep, which could also be applied to goats. This includes assessment of behavior, vision (by testing of the menace response), pruritus (by testing the response to scratching), and movement (with and without blindfolding). This may lead to a more detailed neurologic examination&#160;of reporting animals as scrapie suspects. It&#160;could also be used in experimental TSE studies of sheep or goats to evaluate disease progression or to identify clinical end-point.

A short clinical examination protocol is presented to aid in the detection of classical and atypical scrapie in sheep and goats.

The diagnosis of scrapie, a transmissible spongiform encephalopathy (TSEs) of sheep and goats, is currently based on the detection of disease-associated ...

A Multi-Modal Approach to Assessing Recovery in Youth Athletes Following Concussion

Concussion is one of the most commonly reported injuries amongst children and youth involved in sport participation. Following a concussion, youth can experience a range of short and long term neurobehavioral symptoms (somatic, cognitive and emotional/behavioral) that can have a significant impact on one&#8217;s participation in daily activities and pursuits of interest (e.g., school, sports, work, family/social life, etc.). Despite this, there remains a paucity in clinically driven research aimed specifically at exploring concussion within the youth sport population, and more specifically, multi-modal approaches to measuring recovery. This article provides an overview of a novel and multi-modal approach to measuring recovery amongst youth athletes following concussion. The presented approach involves the use of both pre-injury/baseline testing and post-injury/follow-up testing to assess performance across a wide variety of domains (post-concussion symptoms, cognition, balance, strength, agility/motor skills and resting state heart rate variability). The goal of this research is to gain a more objective and accurate understanding of recovery following concussion in youth athletes (ages 10-18 years). Findings from this research can help to inform the development and use of improved approaches to concussion management and rehabilitation specific to the youth sport community.

This article provides an overview of a multi-modal approach to assessing recovery following concussion in youth athletes. The described protocol uses pre- and post-concussion assessment of performance across a wide variety of domains and can inform the development of improved concussion rehabilitation protocols specific to the youth sport community.

Concussion is one of the most commonly reported injuries amongst children and youth involved in sport participation. Following a concussion, youth can ...

Echocardiographic and Histological Examination of Cardiac Morphology in the Mouse

An increasing number of genetically modified mouse models has become available in recent years. Moreover, the number of pharmacological studies performed in mice is high. Phenotypic characterization of these mouse models also requires the examination of cardiac function and morphology. Echocardiography and magnetic resonance imaging (MRI) are commonly used approaches to characterize cardiac function and morphology in mice. Echocardiographic and MRI equipment specialized for use in small rodents is&#160;expensive and requires a dedicated space. This protocol describes cardiac measurements in mice using a clinical echocardiographic system with a 15 MHz human vascular probe. Measurements are performed on anesthetized adult mice. At least three image sequences are recorded and analyzed for each animal in M-mode in the parasternal short-axis view. Afterwards, cardiac histological examination is performed, and cardiomyocyte diameters are determined on hematoxylin-eosin- or wheat germ agglutinin (WGA)-stained paraffin sections. Vessel density is determined morphometrically after Pecam-1 immunostaining. The protocol has been applied successfully to pharmacological studies and different genetic animal models under baseline conditions, as well as after experimental myocardial infarction by the permanent ligation of the left anterior descending coronary artery (LAD). In our experience, echocardiographic investigation is limited to anesthetized animals and is feasible in adult mice weighing at least 25 g.

Echocardiographic examination is frequently used in mice. Expensive high-resolution ultrasound devices have been developed for this purpose. This protocol describes an affordable echocardiographic procedure combined with histological morphometric analyses to determine cardiac morphology.

An increasing number of genetically modified mouse models has become available in recent years. Moreover, the number of pharmacological studies performed ...

An In Vitro Approach to Photodynamic Therapy

Photodynamic therapy (PDT) is a medical procedure that involves incubation of an exogenously applied photosensitizer (PS) followed by visible light photoactivation to induce cell apoptosis. The Federal Drug Administration has approved PDT for the treatment of actinic keratosis, and clinical guidelines recommend PDT as a treatment for certain non-melanoma skin cancers and acne vulgaris. PDT is an advantageous therapeutic modality as it is low cost, non-invasive, and associated with minimal adverse events and scaring. In the first step of PDT, a PS is applied and allowed to accumulate intracellularly. Subsequent light irradiation induces reactive oxygen species formation, which may ultimately lead to cell apoptosis, membrane disruption, mitochondrial damage, immune modulation, keratinocyte proliferation, and collagen turnover. Herein, we present an in vitro method to study PDT in an adherent cell line. This treatment protocol is designed to simulate PDT and may be adjusted to studying the use of PDT with various cell lines, photosensitizers, incubation temperatures, or photoactivation wavelengths. Squamous cell carcinoma cells were incubated with 0, 0.5, 1.0, and 2 mM 5-aminolevulinic acid (5-ALA) for 30 min and photoactivated with 417 nm blue light for 1,000 s. The primary outcome measure was apoptosis and necrosis, as measured by annexin-V and 7-aminoactinomycin D flow cytometry. There was a dose-dependent increase in cell apoptosis following thirty-minute incubation of 5-ALA. To achieve high inter-test validity, it is important to maintain consistent incubation and light parameters when performing in vitro PDT experiments. PDT is a useful clinical procedure and in vitro research may allow for the development of novel PSs, optimization of protocols, and new indications for PDT.

An In Vitro Approach to Photodynamic Therapy

Photodynamic therapy (PDT) is a medical procedure that involves incubation of an exogenously applied photosensitizer (PS) followed by visible light photoactivation to induce apoptosis. We present an in vitro PDT protocol designed to simulate PDT that may be used to study differences in PS incubation and light treatment parameters.

Photodynamic therapy (PDT) is a medical procedure that involves incubation of an exogenously applied photosensitizer (PS) followed by visible light ...

A Metadata Extraction Approach for Clinical Case Reports to Enable Advanced Understanding of Biomedical Concepts

Clinical case reports (CCRs) are a valuable means of sharing observations and insights in medicine. The form of these documents varies, and their content includes descriptions of numerous, novel disease presentations and treatments. Thus far, the text data within CCRs is largely unstructured, requiring significant human and computational effort to render these data useful for in-depth analysis. In this protocol, we describe methods for identifying metadata corresponding to specific biomedical concepts frequently observed within CCRs. We provide a metadata template as a guide for document annotation, recognizing that imposing structure on CCRs may be pursued by combinations of manual and automated effort. The approach presented here is appropriate for organization of concept-related text from a large literature corpus (e.g., thousands of CCRs) but may be easily adapted to facilitate more focused tasks or small sets of reports. The resulting structured text data includes sufficient semantic context to support a variety of subsequent text analysis workflows: meta-analyses to determine how to maximize CCR detail, epidemiological studies of rare diseases, and the development of models of medical language may all be made more realizable and manageable through the use of structured text data.

We present a protocol and associated metadata template for the extraction of text describing biomedical concepts in clinical case reports. The structured text values produced through this protocol can support deep analysis of thousands of clinical narratives.

Clinical case reports (CCRs) are a valuable means of sharing observations and insights in medicine. The form of these documents varies, and their content ...

A Novel Approach to Monitoring Graft Neovascularization in the Human Gingiva

Laser speckle contrast imaging (LSCI) is a novel method for measuring superficial blood perfusion over large areas. Since it is non-invasive and avoids direct contact with the measured area, it is suitable for monitoring blood flow changes during wound healing in human patients. Vestibuloplasty is periodontal surgery to the oral vestibule, aiming to restore vestibular depth with simultaneous enlargement of the keratinized gingiva. In this special clinical case, a split thickness flap was elevated at the first upper premolar and a xenogenic collagen matrix was adapted to the resulting recipient bed. LSCI was used to monitor the re- and neovascularization of the graft and the surrounding mucosa for one year. A protocol is introduced for the correct adjustment of microcirculation measurement in the oral mucosa, highlighting difficulties and possible failures.
The clinical case study presented demonstrated that &#8212; following the appropriate protocol &#8212; LSCI is a suitable and reliable method for following up microcirculation in a healing wound in the human oral mucosa and gives useful information on graft integration.

This study introduces a protocol for measuring microcirculation in human oral mucosa by laser speckle contrast imaging. The monitoring of wound healing after vestibuloplasty combined with a xenogenic collagen graft is presented on a clinical case.

Laser speckle contrast imaging (LSCI) is a novel method for measuring superficial blood perfusion over large areas. Since it is non-invasive and avoids ...

Transthoracic Echocardiographic Examination in the Rabbit Model

Large animal models such as the rabbit are valuable for translational preclinical research. Rabbits have a similar cardiac electrophysiology compared to that of humans and that of other large animal models such as dogs and pigs. However, the rabbit model has the additional advantage of lower maintenance costs compared to other large animal models. The longitudinal evaluation of cardiac function using echocardiography, when appropriately implemented, is a useful methodology for preclinical assessment of novel therapies for heart failure with reduced ejection fraction (e.g. cardiac regeneration). The correct use of this non-invasive tool requires the implementation of a standardized examination protocol following international guidelines. Here we describe, step by step, a detailed protocol supervised by veterinary cardiologists for performing echocardiography in the rabbit model, and demonstrate how to correctly obtain the different echocardiographic views and imaging planes, as well as the different imaging modes available in a clinical echocardiography system routinely used in human and veterinary patients.

Here we describe, step by step, a detailed protocol for performing echocardiography in the rabbit model. We show how to correctly obtain the different echocardiographic views and imaging planes, as well as the different imaging modes available in a clinical echocardiography system routinely used in human and veterinary patients.

Large animal models such as the rabbit are valuable for translational preclinical research. Rabbits have a similar cardiac electrophysiology compared to ...

Investigating Novel Mechanisms of Microvascular Dysfunction in Humans

Intradermal Microdialysis: An Approach to Investigating Novel Mechanisms of Microvascular Dysfunction in Humans

The cutaneous vasculature is an accessible tissue that can be used to assess microvascular function in humans. Intradermal microdialysis is a minimally invasive technique used to investigate mechanisms of vascular smooth muscle and endothelial function in the cutaneous circulation. This technique allows for the pharmacological dissection of the pathophysiology of microvascular endothelial dysfunction as indexed by decreased nitric oxide-mediated vasodilation, an indicator of cardiovascular disease development risk. In this technique, a microdialysis probe is placed in the dermal layer of the skin, and a local heating unit with a laser Doppler flowmetry probe is placed over the probe to measure the red blood cell flux. The local skin temperature is clamped or stimulated with direct heat application, and pharmacological agents are perfused through the probe to stimulate or inhibit intracellular signaling pathways in order to induce vasodilation or vasoconstriction or to interrogate mechanisms of interest (co-factors, antioxidants, etc.). The cutaneous vascular conductance is quantified, and mechanisms of endothelial dysfunction in disease states can be delineated.

Author Spotlight: A Pharmacodissection Approach to Uncover Mechanisms in Cardiovascular Disease Risk Populations 

Intradermal microdialysis is a minimally invasive technique used to investigate microvascular function in health and disease. Both dose-response and local heating protocols can be utilized for this technique to explore mechanisms of vasodilation and vasoconstriction in the cutaneous circulation.

The cutaneous vasculature is an accessible tissue that can be used to assess microvascular function in humans. Intradermal microdialysis is a minimally ...