Publications by authors named "Chandan Reddy"

77 Publications

Conditioned place preference and spontaneous dorsal horn neuron activity in chronic constriction injury model in rats.

Pain 2015 Dec;156(12):2562-2571

Departments of Neurosurgery Anesthesia and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA.

Patients with neuropathic pain commonly present with spontaneous pain, in addition to allodynia and hyperalgesia. Although evoked responses in neuropathic pain models are well characterized, determining the presence of spontaneous pain is more challenging. We determined whether the chronic constriction injury (CCI) model could be used to measure effects of treatment of spontaneous pain, by evaluating dorsal horn neuron (DHN) spontaneous activity and spontaneous pain-related behaviors. We measured conditioned place preference (CPP) to analgesia produced by sciatic nerve block with bupivacaine in rats with established CCI. We undertook another CPP experiment using hind paw incision. We also examined DHN spontaneous activity in CCI rats. Although CCI produced nocifensive responses to mechanical stimuli, CPP to analgesic nerve block was not evident 14 days after injury: Compared with baseline (314 ± 65 seconds), CCI rats did not show a preference for the bupivacaine-paired chamber after conditioning (330 ± 102 seconds). However, sciatic nerve block after hind paw incision produced CPP on postoperative day 1, serving as a positive control. The proportion of spontaneously active DHNs (33%) was not significantly increased in CCI rats compared with the sham (21%). The median rate of spontaneous activity in the CCI group (12.6 impulses per second) was not different from the sham group (9.2 impulses per second). Also, there was no change in DHN spontaneous activity after sciatic nerve block with bupivacaine. Our findings suggest that CCI as a neuropathic pain model should not be used to measure effects of treatment of spontaneous pain driven by the peripheral input.
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http://dx.doi.org/10.1097/j.pain.0000000000000365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4715376PMC
December 2015

Predicting gene functions from multiple biological sources using novel ensemble methods.

Int J Data Min Bioinform 2015 ;12(2):184-206

The functional classification of genes plays a vital role in molecular biology. Detecting previously unknown role of genes and their products in physiological and pathological processes is an important and challenging problem. In this work, information from several biological sources such as comparative genome sequences, gene expression and protein interactions are combined to obtain robust results on predicting gene functions. The information in such heterogeneous sources is often incomplete and hence making the maximum use of all the available information is a challenging problem. We propose an algorithm that improves the performance of prediction of different models built on individual sources. We also develop a heterogeneous boosting framework that uses all the available information even if some sources do not provide any information about some of the genes. We demonstrate the superior performance of the proposed methods in terms of accuracy and F-measure compared to several imputation and integration schemes.
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http://dx.doi.org/10.1504/ijdmb.2015.069418DOI Listing
November 2015

Diagnostic Yield of FDG-PET/CT, MRI, and CSF Cytology in Non-Biopsiable Neurolymphomatosis as a Heralding Sign of Recurrent Non-Hodgkin's Lymphoma.

Cureus 2015 Sep 9;7(9):e319. Epub 2015 Sep 9.

Department of Radiology, University of Iowa Hospitals and Clinics.

Neurolymphomatosis (NL) is a rare condition associated with lymphomas in which various structures of the nervous system are infiltrated by malignant lymphocytes. Rarely, it may be the presenting feature of recurrence of lymphoma otherwise deemed to be in remission. It is crucial, as is the case with all types of nodal or visceral involvement of lymphoma, to identify the disease early and initiate treatment with chemotherapy and/or radiation therapy. Positron emission tomography-computed tomography (PET-CT) has been shown to be a sensitive modality for staging, restaging, biopsy guidance, therapy response assessment, and surveillance for recurrence of lymphoma. Magnetic resonance imaging (MRI) is another useful imaging modality, which, along with PET/CT, compliment cerebrospinal spinal fluid (CSF) cytology and electromyography (EMG) in the diagnosis of NL. Performing nerve biopsies to confirm neurolymphomatosis can be challenging and with associated morbidity. The case presented herein illustrates the practical usefulness of these tests in detecting NL as a heralding feature of lymphoma recurrence, especially in the absence of histopathologic correlation.
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http://dx.doi.org/10.7759/cureus.319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601979PMC
September 2015

Kinematic analysis of the gait of adult sheep during treadmill locomotion: Parameter values, allowable total error, and potential for use in evaluating spinal cord injury.

J Neurol Sci 2015 Nov 21;358(1-2):107-12. Epub 2015 Aug 21.

Department of Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.

We are developing a novel intradural spinal cord (SC) stimulator designed to improve the treatment of intractable pain and the sequelae of SC injury. In-vivo ovine models of neuropathic pain and moderate SC injury are being implemented for pre-clinical evaluations of this device, to be carried out via gait analysis before and after induction of the relevant condition. We extend previous studies on other quadrupeds to extract the three-dimensional kinematics of the limbs over the gait cycle of sheep walking on a treadmill. Quantitative measures of thoracic and pelvic limb movements were obtained from 17 animals. We calculated the total-error values to define the analytical performance of our motion capture system for these kinematic variables. The post- vs. pre-injury time delay between contralateral thoracic and pelvic-limb steps for normal and SC-injured sheep increased by ~24s over 100 steps. The pelvic limb hoof velocity during swing phase decreased, while range of pelvic hoof elevation and distance between lateral pelvic hoof placements increased after SC injury. The kinematics measures in a single SC-injured sheep can be objectively defined as changed from the corresponding pre-injury values, implying utility of this method to assess new neuromodulation strategies for specific deficits exhibited by an individual.
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http://dx.doi.org/10.1016/j.jns.2015.08.031DOI Listing
November 2015

Combined common peroneal and tibial nerve injury after knee dislocation: one injury or two? An MRI-clinical correlation.

Neurosurg Focus 2015 Sep;39(3):E8

Departments of 2 Neurologic Surgery and.

OBJECT Knee dislocations are often accompanied by stretch injuries to the common peroneal nerve (CPN). A small subset of these injuries also affect the tibial nerve. The mechanism of this combined pattern could be a single longitudinal stretch injury of the CPN extending to the sciatic bifurcation (and tibial division) or separate injuries of both the CPN and tibial nerve, either at the level of the tibiofemoral joint or distally at the soleal sling and fibular neck. The authors reviewed cases involving patients with knee dislocations with CPN and tibial nerve injuries to determine the localization of the combined injury and correlation between degree of MRI appearance and clinical severity of nerve injury. METHODS Three groups of cases were reviewed. Group 1 consisted of knee dislocations with clinical evidence of nerve injury (n = 28, including 19 cases of complete CPN injury); Group 2 consisted of knee dislocations without clinical evidence of nerve injury (n = 19); and Group 3 consisted of cases of minor knee trauma but without knee dislocation (n = 14). All patients had an MRI study of the knee performed within 3 months of injury. MRI appearance of tibial and common peroneal nerve injury was scored by 2 independent radiologists in 3 zones (Zone I, sciatic bifurcation; Zone II, knee joint; and Zone III, soleal sling and fibular neck) on a severity scale of 1-4. Injury signal was scored as diffuse or focal for each nerve in each of the 3 zones. A clinical score was also calculated based on Medical Research Council scores for strength in the tibial and peroneal nerve distributions, combined with electrophysiological data, when available, and correlated with the MRI injury score. RESULTS Nearly all of the nerve segments visualized in Groups 1 and 2 demonstrated some degree of injury on MRI (95%), compared with 12% of nerve segments in Group 3. MRI nerve injury scores were significantly more severe in Group 1 relative to Group 2 (2.06 vs 1.24, p < 0.001) and Group 2 relative to Group 3 (1.24 vs 0.13, p < 0.001). In both groups of patients with knee dislocations (Groups 1 and 2), the MRI nerve injury score was significantly higher for CPN than tibial nerve (2.72 vs 1.40 for Group 1, p < 0.001; 1.39 vs 1.09 for Group 2, p < 0.05). The clinical injury score had a significantly strong correlation with the MRI injury score for the CPN (r = 0.75, p < 0.001), but not for the tibial nerve (r = 0.07, p = 0.83). CONCLUSIONS MRI is highly sensitive in detecting subclinical nerve injury. In knee dislocation, clinical tibial nerve injury is always associated with simultaneous CPN injury, but tibial nerve function is never worse than peroneal nerve function. The point of maximum injury can occur in any of 3 zones.
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http://dx.doi.org/10.3171/2015.6.FOCUS15125DOI Listing
September 2015

A survey on platforms for big data analytics.

J Big Data 2015;2(1). Epub 2014 Oct 9.

Department of Computer Science, Wayne State University, Detroit, MI 48202 USA.

The primary purpose of this paper is to provide an in-depth analysis of different platforms available for performing big data analytics. This paper surveys different hardware platforms available for big data analytics and assesses the advantages and drawbacks of each of these platforms based on various metrics such as scalability, data I/O rate, fault tolerance, real-time processing, data size supported and iterative task support. In addition to the hardware, a detailed description of the software frameworks used within each of these platforms is also discussed along with their strengths and drawbacks. Some of the critical characteristics described here can potentially aid the readers in making an informed decision about the right choice of platforms depending on their computational needs. Using a star ratings table, a rigorous qualitative comparison between different platforms is also discussed for each of the six characteristics that are critical for the algorithms of big data analytics. In order to provide more insights into the effectiveness of each of the platform in the context of big data analytics, specific implementation level details of the widely used k-means clustering algorithm on various platforms are also described in the form pseudocode.
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http://dx.doi.org/10.1186/s40537-014-0008-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505391PMC
October 2014

Malignant peripheral nerve sheath tumor arising in the setting of cervical nerve root schwannomas.

J Clin Neurosci 2015 Oct;22(10):1696-9

Department of Neurosurgery, University of Iowa Hospitals and Clinics, 1426 Ranier Drive, Iowa City, IA 52246, USA.

We present a 23-year-old woman who was diagnosed with a malignant peripheral nerve sheath tumor (MPNST), 17 months following the resection of a schwannoma. MPNST is rare and is usually associated with neurofibromatosis. The typical treatment of resection and radiation is difficult to achieve in the spine.
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http://dx.doi.org/10.1016/j.jocn.2015.05.016DOI Listing
October 2015

Joint impact of clinical and behavioral variables on the risk of unplanned readmission and death after a heart failure hospitalization.

PLoS One 2015 4;10(6):e0129553. Epub 2015 Jun 4.

Center for health policy and health services research, Henry Ford Health System, Detroit, Michigan, United States of America.

Most current methods for modeling rehospitalization events in heart failure patients make use of only clinical and medications data that is available in the electronic health records. However, information about patient-reported functional limitations, behavioral variables and socio-economic background of patients may also play an important role in predicting the risk of readmission in heart failure patients. We developed methods for predicting the risk of rehospitalization in heart failure patients using models that integrate clinical characteristics with patient-reported functional limitations, behavioral and socio-economic characteristics. Our goal was to estimate the predictive accuracy of the joint model and compare it with models that make use of clinical data alone or behavioral and socio-economic characteristics alone, using real patient data. We collected data about the occurrence of hospital readmissions from a cohort of 789 heart failure patients for whom a range of clinical and behavioral characteristics data is also available. We applied the Cox model, four different variants of the Cox proportional hazards framework as well as an alternative non-parametric approach and determined the predictive accuracy for different categories of variables. The concordance index obtained from the joint prediction model including all types of variables was significantly higher than the accuracy obtained from using only clinical factors or using only behavioral, socioeconomic background and functional limitations in patients as predictors. Collecting information on behavior, patient-reported estimates of physical limitations and frailty and socio-economic data has significant value in the predicting the risk of readmissions with regards to heart failure events and can lead to substantially more accurate events prediction models.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0129553PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456390PMC
May 2016

Prolongation of F-wave minimal latency: a sensitive predictor of polyneuropathy.

Int J Neurosci 2016 Jun 5;126(6):520-525. Epub 2015 Aug 5.

a Department of Neurology , Carver College of Medicine, The University of Iowa , Iowa City , IA , USA.

Introduction: To evaluate the sensitivity of F-wave minimal latencies, we compared F-waves with motor and sensory nerve conduction studies (MNCS and SNCS) in patients with peripheral neuropathy.

Methods: A retrospective chart review conducted in 484 patients confirmed the clinical evidence of a polyneuropathy, and studies of F-wave minimal latencies as well as MNCS and SNCS in each patient.

Results: Overall rate of abnormality reached 469/484 (96.9%) for F-wave minimal latencies as compared to 374/484 (77%) for nerve conduction studies ( p < 0.0001). Nerve-specific abnormalities of F-waves showed 290/354 (82%), 140/171 (82%), 367/398 (92%) and 357/376 (95%) for median, ulnar, peroneal and tibial nerves, respectively. Corresponding values for MNCS consisted of 108/354 (31%), 29/171 (17%), 258/398 (65%) and 189/376 (50%) (all p < 0.0001). In contrast, SNCS revealed abnormalities in 120/333 (36%), 60/159 (38%) and 266/474 (56%) of median, ulnar and sural nerves.

Conclusion: F-wave minimal latencies serve as the best predictor of polyneuropathy followed by SNCS and then MNCS.
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http://dx.doi.org/10.3109/00207454.2015.1040492DOI Listing
June 2016

Sphenopalatine ganglion electrical nerve stimulation implant for intractable facial pain.

Pain Physician 2015 May-Jun;18(3):E403-9

University of Iowa, Dept. of Anesthesiology, Iowa City, Iowa.

Persistent idiopathic facial pain can be extremely difficult and significantly challenging to manage for the patient and the clinician. Pharmacological treatment of these painful conditions is not always successful. It has been suggested that the autonomic reflex plays an important role in the pathophysiology of headaches and facial neuralgia. The key structure in the expression of cranial autonomic symptoms is the sphenopalatine ganglion (SPG), also known as the pterygopalatine ganglion. The role of the SPG in the pathophysiology of headaches and facial pain has become clearer in the past decade. In this case report, we describe a 30 year-old woman with insidious onset of right facial pain. She was suffering from daily pain for more than 9 years prior to her visit at the pain clinic. Her pain was constant with episodic aggravation without a predisposing trigger factor. The patient was evaluated by multiple different specialties and tried multimodal therapy, which included antiepileptic medications, with minimal pain relief. A SPG block using short-acting local anesthetic provided significant temporary pain relief. The second and third attempt of SPG block using different local anesthetic medications demonstrated the same responses. After a thorough psychological assessment and ruling out the presence of a correctable cause for the pain, we decided to proceed with SPG electrical neuromodulation. The patient reported significant pain relief during the electrical nerve stimulation trial. The patient underwent a permanent implant of the neurostimulation electrode in the SPG region. The patient was successfully taken off opioid medication and her pain was dramatically responsive during a 6 month follow-up visit. In this article we describe the SPG nerve stimulation and the technical aspect of pterygopalatine fossa electrode placement. The pterygoplatine fossa is an easily accessible location. This case report will be encouraging for physicians treating intractable facial pain by demonstrating a novel therapeutic option. This report shows a minimally invasive approach to the SPG.
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December 2015

A Unique Case of Primary Ewing's Sarcoma of the Cervical Spine in a 53-Year-Old Male: A Case Report and Review of the Literature.

Case Rep Med 2015 23;2015:402313. Epub 2015 Feb 23.

Department of Neurosurgery, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52246, USA.

Extraskeletal Ewing's sarcoma (EES) is a rare presentation, representing only 15% of all primary Ewing's sarcoma cases. Even more uncommon is EES presenting as a primary focus in the spinal canal. These rapidly growing tumors often present with focal neurological symptoms of myelopathy or radiculopathy. There are no classic characteristic imaging findings and thus the physician must keep a high index of clinical suspicion. Diagnosis can only be definitively made by histopathological studies. In this report, we discuss a primary cervical spine EES in a 53-year-old man who presented with a two-month history of left upper extremity pain and acute onset of weakness. Imaging revealed a cervical spinal canal mass. After undergoing cervical decompression, histopathological examination confirmed a diagnosis of Ewing's sarcoma. A literature search revealed fewer than 25 reported cases of primary cervical spine EES published in the past 15 years and only one report demonstrating this pathology in a patient older than 30 years of age (age = 38). Given the low incidence of this pathology presenting in this age group and the lack of treatment guidelines, each patient's plan should be considered on a case-by-case basis until further studies are performed to determine optimal evidence based treatment.
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http://dx.doi.org/10.1155/2015/402313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352905PMC
March 2015

Ultrasound guided peripheral nerve stimulation implant for management of intractable pain after inguinal herniorrhaphy.

Pain Physician 2015 Jan-Feb;18(1):E31-8

University of Iowa, Iowa City, Iow.

Background: Inguinal hernia repair is one of the most common operations performed worldwide. Intractable pain following this operation is a potential debilitating complication. The exact etiology of this complex pain is unknown and the treatment of chronic pain after inguinal herniorrhaphy can be a difficult task for both the patient and the clinician.

Objectives: The objectives of this study are to identify the ability of peripheral nerve electrical stimulation to decrease post inguinal herniorrhaphy pain, increase patients' functionality, and decrease pain medication use.

Study Design: Three patients with intractable pain after inguinal herniorrhaphy were included in this case series. Two patients had right-sided inguinal repair and one had a left-sided repair. Pain in these patients all began after the inguinal repair and had an average pain duration of 3.4 years after surgery. All 3 patients had been treated with multiple pain management modalities without significant pain improvement. We will describe the clinical course of these patients who presented with chronic intractable pain. After a period of failed conservative medical management and repetitive successful nerve blocks, we decided to proceed with utilizing electrical nerve stimulation as a treatment modality.

Setting: This retrospective study was done at the university hospital and has an IRB assigned number.

Results: After careful consideration of the patients' history and physical examination and a thorough psychological assessment, we proceeded with a temporary percutaneous electrical neurostimulation that provided significant pain relief. Ultrasound guided permanent percutaneous electrical neurostimulation implant was shown to provide significant pain relief at 12-month follow-ups. We reviewed all existing pertinent medical literature related to the management of post herniorrhaphy pain. This case series adds to our current knowledge for chronic intractable post herniorrhaphy pain management.

Limitations: This study is a retrospective assessment of a new technique that was applied to a limited number of cases. It remains to be determined whether this technique is superior to the classical open surgical technique in the future. Our findings warrant further studies on the utilization of peripheral nerve stimulation with chronic post herniorrhaphy pain.
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November 2015

Efficient Mining of Discriminative Co-clusters from Gene Expression Data.

Knowl Inf Syst 2014 Dec;41(3):667-696

Department of Computer Science, Wayne State University, Detroit, MI, 48202.

Discriminative models are used to analyze the differences between two classes and to identify class-specific patterns. Most of the existing discriminative models depend on using the entire feature space to compute the discriminative patterns for each class. Co-clustering has been proposed to capture the patterns that are correlated in a subset of features, but it cannot handle discriminative patterns in labeled datasets. In certain biological applications such as gene expression analysis, it is critical to consider the discriminative patterns that are correlated only in a subset of the feature space. The objective of this paper is two-fold: first, it presents an algorithm to efficiently find arbitrarily positioned co-clusters from complex data. Second, it extends this co-clustering algorithm to discover discriminative co-clusters by incorporating the class information into the co-cluster search process. In addition, we also characterize the discriminative co-clusters and propose three novel measures that can be used to evaluate the performance of any discriminative subspace pattern mining algorithm. We evaluated the proposed algorithms on several synthetic and real gene expression datasets, and our experimental results showed that the proposed algorithms outperformed several existing algorithms available in the literature.
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http://dx.doi.org/10.1007/s10115-013-0684-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4308820PMC
December 2014

Neuromodulation of the great auricular nerve: a case report.

Neuromodulation 2014 Dec 24;17(8):784-7. Epub 2013 Sep 24.

Center of Pain Medicine and Regional Anesthesia, University of Iowa, Iowa City, IA, USA.

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http://dx.doi.org/10.1111/ner.12114DOI Listing
December 2014

Neuromodulation of the suprascapular nerve.

Pain Physician 2014 Nov-Dec;17(6):E769-73

University of Iowa, Dept. of Anesthesiology, Iowa City, Iowa.

The shoulder joint is an enarthrodial or ball-and-socket joint. A complex network of anatomic structures endows the human shoulder with tremendous mobility, greater than any other joint in the body. Many pathologies can been found in those patients with chronic shoulder pain. The painful limitation of shoulder motion affects hand and arm motion as well; therefore, it significantly influences work performance and everyday activities as well as the quality of life. Therefore, the treatment of patients with chronic shoulder pain has major social and health economic implications. In this article we present a patient with a complex history of shoulder pathology including 7 surgeries that left the patient with chronic debilitating shoulder pain. She was suffering from chronic pain and limited mobility of the shoulder joint due to adhesive shoulder capsulitis. She was treated with a multimodality approach with the goals of increasing shoulder range of motion and decreasing her pain. This did not provide significant improvement. The suprascapular nerve supplies motor and sensory innervation to the shoulder, and can be easily accessible in the supraspinatus fossa. A suprascapular nerve block dramatically decreased her pain. This clinical observation along with confirmatory nerve block play an important role during the decision-making process for a trial period of electrical neuromodulation. She was followed for 3 months after the permanent implantation of a suprascapular nerve stimulator. Her pain and shoulder range of motion in all planes improved dramatically. Peripheral nerve stimulation (PNS) of the suprascapular nerve, in addition to multimodality pain management, is one approach to the difficult task of treating adhesive capsulitis with accompanying pain and the inability to move the shoulder. We conducted a literature review on PubMed and found no case describing a similar patient to our knowledge.
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September 2015

Factors influencing aversion to specific electrodiagnostic studies.

Brain Behav 2014 Sep 22;4(5):698-702. Epub 2014 Jul 22.

Department of Neurology, Carver College of Medicine, The University of Iowa Iowa City, Iowa, USA ; Iowa City Veterans Affairs Medical Center, Department of Neurology Iowa City, Iowa, USA.

Objective: To compare the degree of discomfort caused by nerve conduction studies (NCS) versus needle electromyography (EMG), and to determine what factors predict aversion to one test or the other.

Methods: Two hundred patients underwent both EMG and NCS, and were asked to indicate which test was more uncomfortable. Responses were then correlated with demographic information, testing characteristics, and medical histories to identify any notable associations.

Results: Of the 200 patients, 58.5% (117) of the patients found the NCS more uncomfortable than EMG. Sixty-one percent (11/18) of the younger patients (18-29 years old) found EMG more uncomfortable (P = 0.08), whereas 68% (40/59) of the older patients (age greater than 60 years old) found NCS more uncomfortable (P = 0.05). Sixty-seven percent (14/21) of the patients whose BMI was less than 22 kg/m(2) rated EMG as more uncomfortable (P = 0.01). Sixty-nine percent (27/39) of the patients whose BMI was greater than or equal to 38 found the NCS more uncomfortable (P = 0.02). A positive correlation existed between NCS discomfort and number of nerves tested. 67% (35/52) of the patients with polyneuropathy found NCS more uncomfortable.

Conclusion: Nerve conduction studies are more uncomfortable than needle EMG in the majority of patients, and predictions regarding which test will be more uncomfortable for a given patient are possible.
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http://dx.doi.org/10.1002/brb3.240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188363PMC
September 2014

Venipuncture-induced complex regional pain syndrome: a case report and review of the literature.

Case Rep Med 2014 19;2014:613921. Epub 2014 Aug 19.

Department of Neurosurgery, University of Iowa, Iowa City, IA, USA.

Venipuncture, the most frequently performed invasive medical procedure, is usually benign. Generally it produces only transitory mild discomfort. Venipuncture-induced neuropathic pain is hard to recognize at an early stage. Medical literature reviews show that there is not adequate medical knowledge about this important subject. The inciting incident in complex regional pain syndrome (CRPS) can often seem far too trivial to result in a condition with such severe pathophysiologic effects. The practicing physician has little information available to enable early recognition of the condition, initiation of multidisciplinary treatment modalities, and proper referral to pain specialists. We encountered a unique case of venipuncture-induced complex regional pain syndrome (CRPS). The patient is a 52-year-old school teacher with no significant past medical history, who presented initially to the Center of Pain Medicine with left upper extremity pain. The pain started while phlebotomy was performed in the patient's left antecubital area for routine blood check. The patient's pain did not improve with multiple medications, physical therapy, or several nerve blocks. The patient demonstrated all the signs and symptoms of chronic neuropathic pain of CRPS in the upper extremity with minimal response to the continuous pain management. We decided to proceed with cervical spinal cord nerve stimulation along with continuing other modalities. The patient responded to this combination. During the follow-up, we noticed that the patient's pain course was complicated by extension of the CRPS to her lower extremity. We will describe the course of treatment for the patient in this paper. In this paper we will discuss the electrical neuromodulation as an important modality in addition to the multidisciplinary pain management for a patient with venipuncture-induced chronic neuropathic pain.
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http://dx.doi.org/10.1155/2014/613921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156992PMC
September 2014

Clinical Reasoning: A 47-year-old woman with left shoulder pain after a fall.

Neurology 2014 Sep;83(11):e112-6

From the Departments of Neurology (N.U.J., L.G.), Neurosurgery (C.G.R.), Neuroradiology (T.M.), and Pathology (L.A.B., C.H.), Carver College of Medicine, University of Iowa, Iowa City.

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http://dx.doi.org/10.1212/WNL.0000000000000776DOI Listing
September 2014

High cervical epidural neurostimulation for post-traumatic headache management.

Pain Physician 2014 Jul-Aug;17(4):E537-41

University of Iowa, Iowa City, Iowa.

Headache following head injuries has been reported for centuries. The majority of post-traumatic headache (PTH) patients will report resolution of their complaints within a few months from the time of the initial injury. PTHs can contribute to disability, lost productivity, and health care costs. In this article we discuss a 40-year-old male with a history of motor vehicle accident and basal skull fracture. The patient had no headache history prior to the accident. He presented with more than 3 years persistent daily headache. The patient described constant throbbing and stabbing quality headaches predominantly on the left hemicranium with constant facial pain. He denies having aura, nausea, or vomiting, but reported occasional neck tightness. An extensive workup was carried out under the direction of the patient's primary neurologist. Secondary to persistent intractable pain, the patient was referred to the pain clinic for further evaluation. As his headaches were resistant to all trialed strategies, we decided to turn our therapeutic focus toward electrical neuromodulation along with continuing multimodal medications and multidisciplinary approach. During 7 days of high cervical dorsal column electrical nerve stimulation trial, he reported almost 90% pain reduction and significant improvement on his quality of life. On 12 months follow-up after he underwent a permanent implant of high cervical dorsal column electrical nerve stimulation, he reported the same level of pain reduction along with 100% satisfaction rate. To the best of our knowledge, there have been no publications to date concerning the application of high cervical nerve stimulation for PTH.
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November 2014

Neuromodulation of the great auricular nerve for persistent post-traumatic headache.

Pain Physician 2014 Jul-Aug;17(4):E531-6

University of Iowa, Iowa City, Iowa.

Headache is the most frequent reason for referral to an outpatient neurology and pain physician practice, with post-traumatic headache (PTH) accounting for approximately 4% of all symptomatic headaches. Headache following trauma has been reported for centuries. In this unique case report we will discuss the clinical course and successful headache treatment of a 57-year-old man diagnosed with PTHs. He suffered from chronic, intractable headaches resistant to multidisciplinary medical management for 4 years. A trial of electrical neuromodulation of the C2-C3 branches within the great auricular nerve (GAN) distribution was proposed as a potential long-term treatment for his chronic, intractable headaches after having several prior headache attacks successfully aborted with ultrasound-guided GAN blocks. Six months after permanent peripheral neurostimulator implantation, the patient reported a greater than 90% reduction in headache frequency, and was able to wean off all his previous prophylactic and abortive headache medications, with the exception of over-the-counter ibuprofen as needed. Subcutaneous electrode application over the branches of C2-C3-namely greater, lesser, and the least occipital nerves-for the treatment of chronic, intractable headache is not a new concept within pain medicine literature. However, subcutaneous electrode application, specifically over the GAN, is unique. The following case report chronicles the novel application of ultrasound-guided peripheral nerve stimulation of the GAN as an effective and safe long-term treatment for chronic, intractable primary headache. The positive outcome chronicled in this case presentation suggests that peripheral nerve stimulation of the GAN should be considered for highly select cases. To our knowledge, this is the first such case report describing GAN as a target for the management of PTH in the literature.
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November 2014

Acute Sciatic Neuritis following Lumbar Laminectomy.

Case Rep Med 2014 15;2014:404386. Epub 2014 Jun 15.

Department of Neurosurgery, University of Iowa, Iowa City, IA, USA.

It is commonly accepted that the common cause of acute/chronic pain in the distribution of the lumbosacral nerve roots is the herniation of a lumbar intervertebral disc, unless proven otherwise. The surgical treatment of lumbar disc herniation is successful in radicular pain and prevents or limits neurological damage in the majority of patients. Recurrence of sciatica after a successful disc surgery can be due to many possible etiologies. In the clinical setting we believe that the term sciatica might be associated with inflammation. We report a case of acute sciatic neuritis presented with significant persistent pain shortly after a successful disc surgery. The patient is a 59-year-old female with complaint of newly onset sciatica after complete pain resolution following a successful lumbar laminectomy for acute disc extrusion. In order to manage the patient's newly onset pain, the patient had multiple pain management visits which provided minimum relief. Persistent sciatica and consistent physical examination findings urged us to perform a pelvic MRI to visualize suspected pathology, which revealed right side sciatic neuritis. She responded to the electrical neuromodulation. Review of the literature on sciatic neuritis shows this is the first case report of sciatic neuritis subsequent to lumbar laminectomy.
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http://dx.doi.org/10.1155/2014/404386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082899PMC
July 2014

Mental nerve neuropathy following dental extraction.

Pain Physician 2014 May-Jun;17(3):E375-80

University of Iowa, Iowa City,IA; and Southeast Rehabilitation Health Center, Des Moines, IA.

Mental nerve neuropathy (MNN), colloquially referred to as numb chin syndrome, is an uncommon neurologic condition that may arise secondary to multiple local and systemic etiologies, and may mimic other pain conditions affecting the mandible. Early recognition of mental nerve neuropathy in conjunction with accurate etiologic identification is crucial, as early pain management may prevent the transition from an acute to a chronic pain condition. In this article, we will describe the clinical courses of 2 patients who presented to the pain clinic with chronic painful numbness in the mental nerve sensory distribution following dental extraction. After a period of failed conservative medical management and repetitive successful nerve blocks at the mental foramen, we decided to proceed with radiofrequency nerve ablation. In both cases, performance of radiofrequency nerve ablation demonstrated a significant decrease in pain. Within interventional pain medicine, nerve blocks are often utilized to assist with pain generator identification, and resultantly also play an integral role in treatment planning. For instance, nerve blocks are often utilized to establish accurate identification of nerve tissue viability, a preliminary role essential for the determination of whether to proceed with an ablative peripheral nerve procedure. In this article, we will additionally review these important usages of nerve blocks within interventional pain medicine. The objective of our article is to help clinicians identify and properly manage early stage mental nerve neuropathy. Moreover, we aim to advance general medical knowledge of this important pain medicine topic. During the process of preparing this article we reviewed all existing pertinent medical literature related to MNN.
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June 2015

Teaching NeuroImages: intraneural ganglion cyst of the tibial nerve.

Neurology 2014 May;82(20):e174-5

From the Departments of Neurology (N.U.J.), Orthopedics and Rehabilitation (J.J.C., B.J.M.), and Neurosurgery (C.G.R.), University of Iowa Hospitals and Clinics, Iowa City.

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http://dx.doi.org/10.1212/WNL.0000000000000429DOI Listing
May 2014

Comparison of spinal cord stimulation profiles from intra- and extradural electrode arrangements by finite element modelling.

Med Biol Eng Comput 2014 Jun 27;52(6):531-8. Epub 2014 Apr 27.

Department of Mechanical Engineering, University of Virginia, Charlottesville, VA, 22903, USA.

Spinal cord stimulation currently relies on extradural electrode arrays that are separated from the spinal cord surface by a highly conducting layer of cerebrospinal fluid. It has recently been suggested that intradural placement of the electrodes in direct contact with the pial surface could greatly enhance the specificity and efficiency of stimulation. The present computational study aims at quantifying and comparing the electrical current distributions as well as the spatial recruitment profiles resulting from extra- and intra-dural electrode arrangements. The electrical potential distribution is calculated using a 3D finite element model of the human thoracic spinal canal. The likely recruitment areas are then obtained using the potential as input to an equivalent circuit model of the pre-threshold axonal response. The results show that the current threshold to recruitment of axons in the dorsal column is more than an order of magnitude smaller for intradural than extradural stimulation. Intradural placement of the electrodes also leads to much higher contrast between the stimulation thresholds for the dorsal root entry zone and the dorsal column, allowing better focusing of the stimulus.
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http://dx.doi.org/10.1007/s11517-014-1157-7DOI Listing
June 2014

Successful conservative management of an intrathecal catheter-associated inflammatory mass.

Spine J 2013 Nov 28;13(11):1708-9. Epub 2013 Oct 28.

Department of Neurosurgery, University of Iowa, 200 West Hawkins Dr., Iowa City, IA 52242, USA.

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http://dx.doi.org/10.1016/j.spinee.2013.07.471DOI Listing
November 2013

UTOPIAN: user-driven topic modeling based on interactive nonnegative matrix factorization.

IEEE Trans Vis Comput Graph 2013 Dec;19(12):1992-2001

Georgia Institute of Technology.

Topic modeling has been widely used for analyzing text document collections. Recently, there have been significant advancements in various topic modeling techniques, particularly in the form of probabilistic graphical modeling. State-of-the-art techniques such as Latent Dirichlet Allocation (LDA) have been successfully applied in visual text analytics. However, most of the widely-used methods based on probabilistic modeling have drawbacks in terms of consistency from multiple runs and empirical convergence. Furthermore, due to the complicatedness in the formulation and the algorithm, LDA cannot easily incorporate various types of user feedback. To tackle this problem, we propose a reliable and flexible visual analytics system for topic modeling called UTOPIAN (User-driven Topic modeling based on Interactive Nonnegative Matrix Factorization). Centered around its semi-supervised formulation, UTOPIAN enables users to interact with the topic modeling method and steer the result in a user-driven manner. We demonstrate the capability of UTOPIAN via several usage scenarios with real-world document corpuses such as InfoVis/VAST paper data set and product review data sets.
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http://dx.doi.org/10.1109/TVCG.2013.212DOI Listing
December 2013

Systems analysis reveals a transcriptional reversal of the mesenchymal phenotype induced by SNAIL-inhibitor GN-25.

BMC Syst Biol 2013 Sep 3;7:85. Epub 2013 Sep 3.

Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, John R, HWCRC 732, Detroit, MI, 4100, USA.

Background: HMLEs (HMLE-SNAIL and Kras-HMLE, Kras-HMLE-SNAIL pairs) serve as excellent model system to interrogate the effect of SNAIL targeted agents that reverse epithelial-to-mesenchymal transition (EMT). We had earlier developed a SNAIL-p53 interaction inhibitor (GN-25) that was shown to suppress SNAIL function. In this report, using systems biology and pathway network analysis, we show that GN-25 could cause reversal of EMT leading to mesenchymal-to-epithelial transition (MET) in a well-recognized HMLE-SNAIL and Kras-HMLE-SNAIL models.

Results: GN-25 induced MET was found to be consistent with growth inhibition, suppression of spheroid forming capacity and induction of apoptosis. Pathway network analysis of mRNA expression using microarrays from GN-25 treated Kras-HMLE-SNAIL cells showed an orchestrated global re-organization of EMT network genes. The expression signatures were validated at the protein level (down-regulation of mesenchymal markers such as TWIST1 and TWIST2 that was concurrent with up-regulation of epithelial marker E-Cadherin), and RNAi studies validated SNAIL dependent mechanism of action of the drug. Most importantly, GN-25 modulated many major transcription factors (TFs) such as inhibition of oncogenic TFs Myc, TBX2, NR3C1 and led to enhancement in the expression of tumor suppressor TFs such as SMAD7, DD1T3, CEBPA, HOXA5, TFEB, IRF1, IRF7 and XBP1, resulting in MET as well as cell death.

Conclusions: Our systems and network investigations provide convincing pre-clinical evidence in support of the clinical application of GN-25 for the reversal of EMT and thereby reducing cancer cell aggressiveness.
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http://dx.doi.org/10.1186/1752-0509-7-85DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848843PMC
September 2013

Intracranial somatosensory responses with direct spinal cord stimulation in anesthetized sheep.

PLoS One 2013 15;8(2):e56266. Epub 2013 Feb 15.

Department of Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States of America.

The efficacy of spinal cord stimulators is dependent on the ability of the device to functionally activate targeted structures within the spinal cord, while avoiding activation of near-by non-targeted structures. In theory, these objectives can best be achieved by delivering electrical stimuli directly to the surface of the spinal cord. The current experiments were performed to study the influence of different stimulating electrode positions on patterns of spinal cord electrophysiological activation. A custom-designed spinal cord neurostimulator was used to investigate the effects of lead position and stimulus amplitude on cortical electrophysiological responses to spinal cord stimulation. Brain recordings were obtained from subdural grids placed in four adult sheep. We systematically varied the position of the stimulating lead relative to the spinal cord and the voltage delivered by the device at each position, and then examined how these variables influenced cortical responses. A clear relationship was observed between voltage and electrode position, and the magnitude of high gamma-band oscillations. Direct stimulation of the dorsal column contralateral to the grid required the lowest voltage to evoke brain responses to spinal cord stimulation. Given the lower voltage thresholds associated with direct stimulation of the dorsal column, and its possible impact on the therapeutic window, this intradural modality may have particular clinical advantages over standard epidural techniques now in routine use.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0056266PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3574132PMC
August 2013

A new device concept for directly modulating spinal cord pathways: initial in vivo experimental results.

Physiol Meas 2012 Dec 15;33(12):2003-15. Epub 2012 Nov 15.

Department of Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.

We describe a novel spinal cord (SC) stimulator that is designed to overcome a major shortcoming of existing stimulator devices: their restricted capacity to selectively activate targeted axons within the dorsal columns. This device overcomes that limitation by delivering electrical stimuli directly to the pial surface of the SC. Our goal in testing this device was to measure its ability to physiologically activate the SC and examine its capacity to modulate somatosensory evoked potentials (SSEPs) triggered by peripheral stimulation. In this acute study on adult sheep (n = 7), local field potentials were recorded from a grid placed in the subdural space of the right hemisphere during electrical stimulation of the left tibial nerve and the spinal cord. Large amplitude SSEPs (>200 µV) in response to SC stimulation were consistently obtained at stimulation strengths well below the thresholds inducing neural injury. Moreover, stimulation of the dorsal columns with signals employed routinely by devices in standard clinical use, e.g., 50 Hz, 0.2 ms pulse width, produced long-lasting changes (>4.5 h) in the SSEP patterns produced by subsequent tibial nerve stimulation. The results of these acute experiments demonstrate that this device can be safely secured to the SC surface and effectively activate somatosensory pathways.
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http://dx.doi.org/10.1088/0967-3334/33/12/2003DOI Listing
December 2012