Musculoskeletal Diseases Commons^™

Effectiveness And Safety Of Abobotulinumtoxina In Pediatric Lower Limb Spasticity: A Phase Iv, Prospective, Observational, Multicenter Study, Mark E. Gormley, Edward Dabrowski, Mauricio R. Delgado, Ann Tilton, Asare Christian, Sarah Helen Evans, Anne-Sophie Grandoulier, Jumaah Goldberg

School of Medicine Faculty Publications

Aim: To assess the longitudinal attainment of patient-centered, function-related Goal Attainment Scaling Total (GAS T)-score after repeated abobotulinumtoxinA (AboBoNT-A) injections over a period of up to 30 months and up to 10 cycles. Method: In this prospective observational study, the investigators' clinical practices recruited patients aged 2 to 17 years with pediatric lower limb spasticity (PLLS). GAS T-scores were assessed for each injection, and goals could be redefined at each visit; scores of 50 reflected goal achievement. Adverse events were recorded. Results: Of 210 patients in the effectiveness population, 171 had cerebral palsy and 163 were previously treated with a …

Case Report: Dysphagia In Inclusion Body Myositis Leading To Respiratory And Gastrointestinal Complications, Veroneka Mikhail, James Espinosa, Alan Lucerna

Rowan-Virtua Research Day

Inclusion body Myositis (IBM) stands as a rare and complex neuromuscular disorder (NMD) characterized by progressive muscle weakness and atrophy. Among its cardinal symptoms are dysphagia and respiratory distress, which are the most common cause of death in this disease. While the differential diagnosis of respiratory distress is vast and includes aspiration, pneumonia, acute coronary syndrome, emphysema, and congestive heart failure, a clinician should recognize that respiratory distress can also be secondary to dysphagia in NMDs like IBM and can quickly become life threating. Here we present the case of a 68-year-old female with a history of IBM who presented …

Reevaluating Informed Consent: Integrating Shared Decision-Making Into Spinal Surgery For Better Patient Outcomes., Jeffrey N Wang, Mohamed A Elhakeem, Matthew J Mesimer, Paul G Mastrokostas, Salman Ahmad, Tim Reed, Brandon Klein, Lucas E Bartlett, Adam D Bitterman, Andrew Megas

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Study Design: Narrative review.

Objectives: The objectives of this study were to answer the following questions: (1) What is the quality of informed consent in spine surgery, including both neurosurgery and orthopaedic spine surgery? (2) What limitations impede the ability of surgeons to engage in effective shared decision-making (SDM) and obtain adequate informed consent? (3) What strategies and solutions may improve the quality of informed consent and SDM? (4) What factors decrease the incidence of litigation in spine surgery?

Methods: N/A.

Results: SDM is a collaborative process where patients are involved in their treatment choices through open communication about risks, …

Lower Extremity Weakness In The Setting Of Covid Myositis, Christopher Dellmyer, Frank Wheeler

Rowan-Virtua Research Day

Bilateral lower extremity weakness has numerable causes including stroke, peripheral neuropathy, deconditioning, Guillain-Barre, Multiple Sclerosis, anterior cord syndrome, trauma, spinal epidural abscess and many more. It is imperative however, that we investigate and understand more rare causes of lower extremity weakness. Here we present the case of a 74-year-old female presented to the ED with a complaint of lower extremity weakness due to Covid myositis causing significant bilateral lower extremity weakness.

Case Report: Dysphagia In Inclusion Body Myositis Leading To Respiratory And Gastrointestinal Complications, Veroneka Mikhail, James A. Espinosa, Alan Lucerna

Rowan-Virtua Research Day

Inclusion Body Myositis (IBM) stands as a rare and complex neuromuscular disorder (NMD) characterized by progressive muscle weakness and atrophy. Among its cardinal symptoms are dysphagia and respiratory distress, which are the most common cause of death in this disease. While the differential diagnosis of respiratory distress is vast and includes aspiration, pneumonia, acute coronary syndrome, emphysema, and congestive heart failure, a clinician should recognize that respiratory distress can also be secondary to dysphagia in NMDs like IBM and can quickly become life threating. Here we present the case of a 68-year-old female with a history of IBM who presented …

Utilizing Microwave Ablation In Combination With Vertebroplasty Is An Effective Method In Reducing Cancer Related Back Pain, Disability, And Opioid Use: A Systematic Review And Meta-Analysis, Jonathan Elias, Lothar Vidal, Richard Jermyn

Rowan-Virtua Research Day

Background: It is estimated that metastases from primary malignant neoplasms affect the spine around 30%-70% of the time. Many times, these osteolytic tumors will cause the degradation of the vertebrae, leaving patients in a tremendous amount of pain, disability, and dependence on opioids as analgesics. Microwave ablation (MWA) followed by vertebroplasties (VP) has been a developing treatment for such a condition; however, there are no systematic reviews or meta-analyses examining the method’s effectiveness thus far.

Purpose: This systematic review and meta-analysis analyzes the 4-week and 12-week outcomes of patients with metastatic spinal cancer treated with the combinatorial treatment …

Mapping Sca1 Regional Vulnerabilities Reveals Neural And Skeletal Muscle Contributions To Disease, Lisa Duvick, W Michael Southern, Kellie A Benzow, Zoe N Burch, Hillary P Handler, Jason S Mitchell, Hannah Kuivinen, Udaya Gadiparthi, Praseuth Yang, Alyssa Soles, Carrie A Sheeler, Orion Rainwater, Shannah Serres, Erin B Lind, Tessa Nichols-Meade, Yun You, Brennon O'Callaghan, Huda Y Zoghbi, Marija Cvetanovic, Vanessa C Wheeler, James M Ervasti, Michael D Koob, Harry T Orr

Duncan NRI Faculty and Staff Publications

Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an expanded polyglutamine tract in the widely expressed ataxin-1 (ATXN1) protein. To elucidate anatomical regions and cell types that underlie mutant ATXN1-induced disease phenotypes, we developed a floxed conditional knockin mouse (f-ATXN1146Q/2Q) with mouse Atxn1 coding exons replaced by human ATXN1 exons encoding 146 glutamines. f-ATXN1146Q/2Q mice manifested SCA1-like phenotypes including motor and cognitive deficits, wasting, and decreased survival. Central nervous system (CNS) contributions to disease were revealed using f-ATXN1146Q/2Q;Nestin-Cre mice, which showed improved rotarod, open field, and Barnes maze performance by 6-12 weeks of age. In contrast, …

Piriformis Syndrome With A Variant Presentation, Roberto Chuapoco, Ryan E. Linford

Annual Research Symposium

Piriformis syndrome has long been a diagnostic quandary due to its tendency to present as other nerve-related conditions. Piriformis syndrome is commonly caused by entrapment of the sciatic nerve as it travels through the greater sciatic foramen due to hypertrophy of the piriformis muscle. However, its constellation of symptoms, including radiating pain down the thigh, can easily be mistaken for lumbosacral radiculopathy. This case report aims to address the misdiagnosis of piriformis syndrome which has prolonged pain for many patients and increased the cost of medical care. It demonstrates a 76-year-old female with a confounding presentation of piriformis syndrome: buttock …

Outpatient Fall Prevention In Ambulatory Adults 65 Years Old And Over, Dorothy L. Osborne-White

Doctor of Nursing Practice (DNP) Scholarly Projects - Archive

Background: In the United States (U.S.), falls are the leading cause of injury among adults 65 and over, resulting in 36 million falls yearly (Moreland et al., 2020). According to the Centers for Disease Control and Prevention (CDC, 2023), one in four older adults experiences a fall each year. Falls are the world's second most prominent cause of accidental deaths (World Health Organization [WHO], 2021). Falls are the leading cause of both fatal and non-fatal injuries among older adults (Moreland et al., 2020).

Methods: A quality improvement project that included a fall bundle was implemented in a primary clinic. A …

Ciprofloxacin-Induced Peripheral Neuropathy: A Case Report, Alexander Refaeian, Eric L. Vest, Michael Schmidt, Jorge D. Guerra, Mohd N. Refaei, Michael Refaeian, Ryan A. Floresca, Manouchehr Refaeian

HCA Healthcare Journal of Medicine

Introduction

Fluoroquinolones, a class of antibiotics, are commonly employed in the treatment of a wide array of bacterial infections. Recognized for their effectiveness against a broad spectrum of pathogens, fluoroquinolones have played a pivotal role in managing conditions like urinary tract infections and respiratory diseases. Nevertheless, their usage is not without contention due to their association with a variety of adverse effects, including tendon rupture and the less frequently reported issue of peripheral neuropathy.

Case Presentation

We present the case of a 42-year-old male who developed peripheral neuropathy several days after completing a 10-day course of ciprofloxacin for gastroenteritis. The …

The Endosomal Escape Vehicle Platform Enhances Delivery Of Oligonucleotides In Preclinical Models Of Neuromuscular Disorders, Xiang Li, Mahboubeh Kheirabadi, Patrick G Dougherty, Kimberli J Kamer, Xiulong Shen, Nelsa L Estrella, Suresh Peddigari, Anushree Pathak, Sara L Blake, Emmanuelle Sizensky, Carmen Del Genio, Arti B Gaur, Mohanraj Dhanabal, Mahasweta Girgenrath, Natarajan Sethuraman, Ziqing Qian

Faculty, Staff and Student Publications

Biological therapeutic agents are highly targeted and potent but limited in their ability to reach intracellular targets. These limitations often necessitate high therapeutic doses and can be associated with less-than-optimal therapeutic activity. One promising solution for therapeutic agent delivery is use of cell-penetrating peptides. Canonical cell-penetrating peptides, however, are limited by low efficiencies of cellular uptake and endosomal escape, minimal proteolytic stability, and toxicity. To overcome these limitations, we designed a family of proprietary cyclic cell-penetrating peptides that form the core of our endosomal escape vehicle technology capable of delivering therapeutic agent-conjugated cargo intracellularly. We demonstrated the therapeutic potential of …

Driving Impairment In Movement Disorders, Karim Makhoul, Joseph Jankovic

Faculty, Staff and Students Publications

BACKGROUND: Driving may be adversely affected by any movement disorder, but has been mostly studied in Parkinson's disease (PD). Few studies have addressed driving impairment in patients with Huntington's disease (HD); driving in other movement disorders such as dystonia, blepharospasm and Tourette syndrome (TS) has not been adequately evaluated.

OBJECTIVES: The aim of this review is to summarize the findings of driving impairment in movement disorders and evaluate the usefulness of clinical tools in guiding clinicians whether to refer patients for driving assessment.

METHODS: A review of literature was performed on PubMed and articles on driving and movement disorders were …

Detection Of Stroke With Retinal Microvascular Density And Self-Supervised Learning Using Oct-A And Fundus Imaging, Samiksha Pachade, Ivan Coronado, Rania Abdelkhaleq, Juntao Yan, Sergio Salazar-Marioni, Amanda Jagolino, Charles Green, Mozhdeh Bahrainian, Roomasa Channa, Sunil A Sheth, Luca Giancardo

Faculty, Staff and Student Publications

Acute cerebral stroke is a leading cause of disability and death, which could be reduced with a prompt diagnosis during patient transportation to the hospital. A portable retina imaging system could enable this by measuring vascular information and blood perfusion in the retina and, due to the homology between retinal and cerebral vessels, infer if a cerebral stroke is underway. However, the feasibility of this strategy, the imaging features, and retina imaging modalities to do this are not clear. In this work, we show initial evidence of the feasibility of this approach by training machine learning models using feature engineering …

Mir-486 Is Essential For Muscle Function And Suppresses A Dystrophic Transcriptome, Adrienne Samani, Rylie M Hightower, Andrea L Reid, Katherine G English, Michael A Lopez, J Scott Doyle, Michael J Conklin, David A Schneider, Marcas M Bamman, Jeffrey J Widrick, David K Crossman, Min Xie, David Jee, Eric C Lai, Matthew S Alexander

Faculty, Staff and Student Publications

miR-486 is a muscle-enriched microRNA, or “myomiR,” that has reduced expression correlated with Duchenne muscular dystrophy (DMD). To determine the function of miR-486 in normal and dystrophin-deficient muscles and elucidate miR-486 target transcripts in skeletal muscle, we characterized mir-486 knockout mice (mir-486 KO). mir-486 KO mice developed disrupted myofiber architecture, decreased myofiber size, decreased locomotor activity, increased cardiac fibrosis, and metabolic defects were exacerbated in mir-486 KO:mdx5cv (DKO) mice. To identify direct in vivo miR-486 muscle target transcripts, we integrated RNA sequencing and chimeric miRNA eCLIP sequencing to identify key transcripts and pathways that contribute towards mir-486 …

Small Rna Signatures Of Acute Ischemic Stroke In L1cam Positive Extracellular Vesicles, Michael A Lopez, Ying Si, Xianzhen Hu, Valentyna Williams, Fuad Qushair, Jackson Carlyle, Lyndsy Alesce, Michael Conklin, Shawn Gilbert, Marcas M Bamman, Matthew S Alexander, Peter H King

Faculty, Staff and Student Publications

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by skeletal muscle instability, progressive muscle wasting, and fibrosis. A major driver of DMD pathology stems from aberrant upregulation of transforming growth factor β (TGFβ) signaling. In this report, we investigated the major transducers of TGFβ signaling, i.e., receptor Smads (R-Smads), in DMD patient skeletal muscle and observed a 48-fold increase in Smad8 mRNA. Smad1, Smad2, Smad3, and Smad5 mRNA were only minimally increased. A similar pattern was observed in the muscle from the mdx5cv mouse. Western blot analysis showed upregulation of phosphorylated Smad1, Smad5, and Smad8 …

Pediatric Nemaline Myopathy: A Systematic Review Using Individual Patient Data, Briana Christophers, Michael A Lopez, Vandana A Gupta, Hannes Vogel, Mary Baylies

Faculty, Staff and Student Publications

Nemaline myopathy is a skeletal muscle disease that affects 1 in 50 000 live births. The objective of this study was to develop a narrative synthesis of the findings of a systematic review of the latest case descriptions of patients with NM. A systematic search of MEDLINE, Embase, CINAHL, Web of Science, and Scopus was performed using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using the keywords pediatric, child, NM, nemaline rod, and rod myopathy. Case studies focused on pediatric NM and published in English between January 1, 2010, and December 31, …

Investigating The Role Of The Skeletal Muscle In Amyotrophic Lateral Sclerosis Neuromuscular Junction Dysfunction, Agnes Badu-Mensah

Electronic Theses and Dissertations, 2020-2023

Neuromuscular junction (NMJ) dysfunction has been identified as one of the earliest events in Amyotrophic Lateral Sclerosis (ALS) pathology. However, which tissue type induces NMJ disruption; be it the motoneurons (hMN), Schwann cells or skeletal muscle (hSKM) remains unresolved. While mechanisms by which ALS hMN contribute to NMJ dysfunction are well-described in literature, limited information exist on how the other tissue types in the tripartite synapse (hSKM and Schwann cells) induce and/or contribute to ALS NMJ disruption. A fair understanding of the role of each tissue type in NMJ dysfunction would help shape the trajectory of future ALS research and …

The Experience Of Off Periods In Parkinson’S Disease: Descriptions, Triggers, And Alleviating Factors, Sneha Mantri, Madeline Lepore, Briana Edison, Margaret Daeschler, Catherine Kopil, Connie Marras, Lana Chahine

Journal of Patient-Centered Research and Reviews

Purpose: Wearing off of Parkinson’s disease medication is common, but triggers and coping strategies for this transient phenomenon are poorly understood. We aimed to assess the lived experience of OFF periods for people with Parkinson’s disease.

Methods: Participants in the longitudinal Fox Insight study who endorsed OFF periods were invited to complete a survey consisting of both multiple-choice and free-text responses. Descriptive statistics were used to summarize multiple-choice responses, and free-text responses were classified into themes through iterative discussion by 3 movement disorders specialists.

Results: A total of 2110 participants (52.4% male) completed the survey. Tremor was the most common …

Use Of Artificial Intelligence To Identify Predictors Of Functional Outcomes In Patients With Facioscapulohumeral Muscular Dystrophy, Natalie K. Katz

Research Days

Background: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common forms of muscular dystrophy characterized by slowly progressive muscle weakness. Symptoms initially involve the facial and shoulder girdle muscles, with later involvement of the distal lower extremities, pelvic girdle and proximal lower extremities. FSHD type 1 (FHSD1) is the most common form (~95% of individuals) and is caused by deletion of microsatellite repeats in the D4Z4 region on chromosome 4 (4q35). Normal individuals have >10 repeats whereas individuals with FSHD1 have 1-10 repeats. There is significant variability in regards to disease severity, rates of progression and functional outcomes, but …

Recurrent Nontuberculous Mycobacterial Tenosynovitis, Melissa Kwan, Richard Tupler

Faculty, Staff and Student Publications

Background: Nontuberculous mycobacteria are an uncommon pathogen for musculoskeletal infection and are difficult to treat because of delays in diagnosis, prolonged treatment requiring both antimycobacterial therapy and surgical debridement, and high rates of resistance to antimycobacterial therapy.

Case Report: We report the case of an 88-year-old male with recurrent Mycobacterium avium complex tenosynovitis despite receiving multiple courses of pharmacologic therapy and surgical debridement.

Conclusion: Nontuberculous mycobacterial musculoskeletal infections can be difficult to diagnose and equally difficult to treat. A combination of antimycobacterial therapy and surgical debridement is often required; however, the rate of treatment failure remains high, particularly with rapidly …

Efficacy And Safety Of Abobotulinumtoxina For Upper Limb Spasticity In Children With Cerebral Palsy: A Randomized Repeat-Treatment Study, Mauricio R. Delgado, Ann Tilton, Jorge Carranzo-Del Rio, Nigar Dursun, Marcin Bonikowski, Resa Aydin, Iwona Maciag-Tymecka, Joyce Oleszek, Edward Dabrowski, Anne-Sophie Grandoulier, Philippe Picaut, The Dysport In Pul Study Group

School of Medicine Faculty Publications

Aim: To assess the efficacy and safety of repeat abobotulinumtoxinA injections in reducing upper limb spasticity in children with cerebral palsy (CP). Method: This was a double-blind, repeat-cycle study (NCT02106351) in children with CP (2–17y). Children were randomized to receive 2U/kg (control), 8U/kg, or 16U/kg abobotulinumtoxinA injections into the target muscle group (wrist or elbow flexors) and additional muscles alongside occupational therapy via a home-exercise therapy program (HETP; minimum five 15min sessions/wk). Children received 8U/kg or 16U/kg plus HETP in cycles 2 to 4. Results: During cycle 1, 210 children (126 males, 84 females; mean age [SD] 9y [4y 5mo], …

Failure To Thrive - An Overlooked Manifestation Of Kmt2b-Related Dystonia: A Case Presentation., Andrew Ng, Serena Galosi, Lisa Salz, Terence Wong, Caitlin Schwager, Shivarajan Amudhavalli, Rose N. Gelineau-Morel, Shimul Chowdhury, Rady Children’S Institute For Genomic Medicine Investigators, Jennifer Friedman

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: KMT2B-related dystonia is a recently described form of childhood onset dystonia that may improve with deep brain stimulation. Prior reports have focused on neurologic features including prominent bulbar involvement without detailing general health consequences that may result from orolingual dysfunction. We describe a family with novel KMT2B mutation with several members with failure to thrive to highlight this non-neurologic, but consequential impact of mutation in this gene.

CASE PRESENTATION: We present a case of a 15-year old female who was admitted and evaluated for failure to thrive. On exam, she had severe speech dysfluency, limited ability to protrude the …

Prevalence And Predictors Of Chronic Pain Intensity And Disability Among Adults With Sickle Cell Disease, Nadine Matthie, Coretta Jenerette, Ashley Gibson, Sudeshna Paul, Melinda Higgins, Lakshmanan Krishnamurti

Faculty, Staff and Student Publications

Among 170 adults with sickle cell disease, we evaluated chronic pain impact and disability prevalence, assessed age and gender differences, and identified psychosocial predictors of chronic pain intensity and disability. Most participants had a high level of disability. Chronic pain intensity and disability were significantly associated with pain catastrophizing and chronic pain self-efficacy, and worsened with age. Further research is needed to confirm study findings and develop interventions, including palliative care approaches that address catastrophizing and disability, particularly for young women and middle-aged adults with sickle cell disease. Moreover, consistent clinical assessment of chronic pain and psychosocial health should be …

Utilization Of A Continuous Pericapsular Nerve Group (Peng) Block With An Opioid-Sparing Repair Of A Femoral Neck Fracture In A Pediatric Patient, Karla Wyatt, Moustafa Zidane, Chyong-Jy Joyce Liu

Faculty, Staff and Students Publications

In the pediatric population, femoral neck fractures are usually associated with high-impact trauma and often present with pain in the groin area. Regional anesthesia can offer adjunctive therapy for acute pain management. Various techniques have been employed to circumvent pain related to hip fractures and resultant hip surgery. Neuraxial, lumbar plexus, caudal, epidural, fascia iliaca, and femoral continuous nerve block techniques are advantageous in mitigating hip pain. However, these approaches require patient repositioning during placement and carry the potential for motor blockade with resultant weakness. A newly described method, the Pericapsular Nerve Group (PENG) block, allows for analgesia of the …

Longitudinal Screening Detects Cognitive Stability And Behavioral Deterioration In Als Patients, Susan Woolley, Ray Goetz, Pam Factor-Litvak, Jennifer Murphy, Jonathan Hupf, Catherine Lomen-Hoerth, Howard Andrews, Daragh Heitzman, Richard Bedlack, Jonathan Katz, Richard Barohn, Eric Sorenson, Bjorn Oskarsson, Americo Fernandes Filho, Edward J. Kasarskis, Tahseen Mozaffar, Sharon Nations, Andrea Swenson, Agnes Koczon-Jaremko, Georgia Christodoulou, Hiroshi Mitsumoto

Neurology Faculty Publications

Objective. To evaluate longitudinal cognitive/behavioral change over 12 months in participants enrolled in the ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS). Methods. We analyzed data from 294 ALS participants, 134 of whom were studied serially. Change over time was evaluated controlling for age, sex, symptom duration, education, race, and ethnicity. Using multiple regression, we evaluated associations among decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores, forced vital capacity (FVC), and cognitive/behavioral changes. Change in cognitive/behavioral subgroups was assessed using one-way analyses of covariance. Results. Participants with follow-up data had fewer baseline behavior problems compared to patients …

Quantitative Ultrasound: Measurement Considerations For The Assessment Of Muscular Dystrophy And Sarcopenia, Michael O. Harris-Love, Reza Monfaredi, Catheeja Ismail, Marc R. Blackman, Kevin Cleary

Exercise and Nutrition Sciences Faculty Publications

Diagnostic musculoskeletal ultrasound has potential clinical utility in characterizing pathological muscle tissue. Sonography has been long proposed as method of assessing muscle damage due to neuromuscular diseases such as muscular dystrophy, and more recently, changes in body and tissue composition associated with muscle wasting disorders such as sarcopenia. The use of quantitative ultrasound as an adjunct diagnostic procedure has different technical challenges than the traditional use of ultrasound in clinical medicine. Operator-dependent technique and variation are critical considerations when obtaining measures of echointensity (i.e., tissue composition estimates) and tissue dimensions (i.e., muscle thickness) – key elements of the ultrasound assessment …