Neurosurgeon-scientists and researchers in the Ohio State University Department of Neurological Surgery are discovering breakthroughs that are transforming the care of patients with neurologic disorders. These are some of the recent research breakthroughs and accomplishments made by our faculty.
Groundbreaking DEFUSE 3 Sedation Study
Dr. Ciarán Powers, surgical director of The Ohio State University’s Comprehensive Stroke Center, recently authored a study examining the impact on type of anesthesia for the patients undergoing mechanical thrombectomy for large vessel occlusion in the groundbreaking DEFUSE 3 study.
Study of Enhanced Recovery After Surgery Protocols
Dr. Francis Farhadi, director, Division of Degenerative and Deformity Spine at The Ohio State University Wexner Medical Center, and colleagues recently demonstrated that intraoperative opioid administration represents an early modifiable predictor of post-operative ileus following spinal surgery. They concluded that potential preventive strategies, implemented as part of enhanced recovery after surgery protocols, could be instituted prior to surgery to reduce its incidence. Learn about this study of enhance recovery after surgery protocols.
Reducing Complications Following Spinal Deformity Correction
Dr. Francis Farhadi, co-director at The Ohio State University Spine Program, and colleagues recently described a novel technique to reduce the risk of a significant complication, termed proximal junctional kyphosis, that can occur following long-segment surgery for spinal deformity correction. The illustration describing the technique was highlighted on the cover of the June 2019 issue of Journal of Neurosurgery Spine.
Confirming Animal Model Use for Study of Post-Brain Injury Immune Suppression
Traumatic injury in children is known to cause immune suppression. Polytrauma involving a brain injury may increase this degree of immune suppression. Dr. Eric Sribnick, Assistant Professor and Pediatric Neurosurgeon, used an animal injury model combining brain injury and hemorrhage to assess immune function after polytrauma. Immune function was measured by whole blood tumor necrosis factor alpha production capacity following incubation with lipopolysaccharide and by measuring the percentage of monocytes. The combined injury correlated with reduced concentration of monocytes and reduced tumor necrosis factor alpha production capacity at post-injury day 1. These results, which demonstrate that this animal model can be used to study post-injury immune suppression, appear in the Journal of Neuroimmunology.
Understanding Risk of Hospital-Acquired Infection of Critical Pediatric Trauma Patients
Assistant Professor and Pediatric Neurosurgeon Dr. Eric Sribnick’s latest research centers on hospital-acquired (nosocomial) infection, a common source of morbidity in critically injured children. Risk factors for nosocomial infection in this population, however, are poorly understood. He hypothesized that critically ill pediatric trauma patients with traumatic brain injury (TBI) would demonstrate higher rates of infection than those without TBI. 203 patients were included in the study, and 27 patients developed an infection. Patients with polytrauma with TBI demonstrated a significantly higher infection rate (30%) than patients with isolated TBI (6%) or traumatic injury without TBI (9%). This update appeared in the journal Pediatric Critical Care Medicine®.
AADC Deficiency Clinical Trial
Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare, inherited disorder that typically appears within the first year of life. Affected infants may have severe developmental delay, and difficulty moving. Currently, there is no cure for AADC deficiency and patients derive little symptomatic benefit from alternative treatments with dopaminergic agonists.
In the laboratory, Krzysztof Bankiewicz, PhD, director of the Center of Brain Health and Performance at The Ohio State University Wexner Medical Center, and colleagues developed the preclinical approach under FDA guidelines that led them to initiate a clinical trial. Phase 1 of the clinical trial has been finalized, in which two different doses were tested in two different cohorts of patients. All subjects are responding remarkably well to the intervention with no adverse effects related to surgical procedure and proceeding gene expression. Learn about this clinical trial.
GDNF Parkinson’s Disease Clinical Trial
Parkinson disease is a neurodegenerative disorder. This progressive disorder affects basal ganglia in the brain, especially the substantia nigra that controls balance and movement. Currently, dopamine-modulated therapies like pharmacological (Levodopa), surgical (deep brain stimulation) or even gene therapy (AAV2-hAADC) are available, but up-to-date, AAV2-GDNF (glial cell line-derived neurotrophic factor) represents the only gene therapy approach that could alter the progression of Parkinson’s disease (PD).
In the laboratory, Krzysztof Bankiewicz, MD, PhD, director of the Center of Brain Health and Performance at The Ohio State University Wexner Medical Center, and colleagues developed the therapeutic platform that led them to initiate a clinical trial under FDA guidance. Currently, they completed at NIH the Phase 1 in advanced PD patients and initiated the Phase 1B that will enroll early and late onset PD patients. Learn about this clinical trial.
Alcohol Addiction Study
FDA-approved medications are often insufficient in sustaining long-term abstinence in treatment-seeking alcoholics (90% of alcoholics relapse at least once during treatment). Krzysztof Bankiewicz, MD, PhD, director of the Center of Brain Health and Performance at The Ohio State University Wexner Medical Center, and colleagues’ current pre-clinical work establishes a new gene therapy paradigm for the treatment of alcohol use disorder that reverses deficits in reward pathway function. In-life observations and post-mortem analysis confirmed that AAV-mediated GDNF treatment attenuates alcohol consumption and reverses chronic alcohol-induced dopamine system dysregulation. Further investigation is currently ongoing to refine dose to optimize therapeutic effect in preventing relapse.
ASM Deficiency Study
Niemann-Pick disease (NPD) is a pediatric lysosomal storage disease that affects lipid metabolism. NPD type A, also called acid sphingomyelinase deficiency, is caused by the deficiency of the acid sphingomyelinase enzyme. Over the years, Lluis Samaranch, PhD, and colleagues developed different therapeutic gene therapy platforms that are currently at different pre-clinical stages:
a) The AAV9 intrathecal approach includes work in knockout mouse model and nonhuman primates. Currently, long-term safety evaluation is ongoing to initiate IND conversations with FDA.
b) The AAV2 direct brain approach is already in conversations with FDA and an IND-enabling long-term safety study is ongoing based on the agency recommendations.
Focused Ultrasound Ablation an Emerging Treatment for Neurological Disorders
Dr. Vibhor Krishna, assistant professor, Department of Neurological Surgery, and colleagues recently performed an imaging-based characterization of ablated tissue (or “lesion”) with early and delayed imaging. They used diffusion MRI to define lesion characteristics associated with good clinical outcomes. This research uncovered the mechanisms underlying the therapeutic efficacy of focused ultrasound ablation (FUSA) that will help researchers develop response biomarkers of therapeutic ablation and eventually make this therapy safer and more effective. Learn more about this study.