Browsing by Author "Dickerman, Rob"
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Item Branched-chain amino acids are neuroprotective against traumatic brain injury and enhance rate of recovery: prophylactic role for contact sports and emergent use(2022) Mathew, Ezek; Williamson, Julie; Mahama-Rodriguez, Alia; Mamo, Lois; Dickerman, RobBackground: Branched-chain amino acids (BCAA) are known to be neurorestorative after traumatic brain injury (TBI). Despite clinically significant improvements in severe TBI patients given BCAA, the approach is largely an unrecognized option. Furthermore, TBI continues to be the most common cause of morbidity and mortality in adolescents and adults. In this study, we sought to demonstrate the neuroprotective and restorative effects of BCAA on the sequelae of TBI. No study has evaluated whether BCAA can be preventive or neuroprotective if taken before a TBI. We hypothesized that if BCAA were elevated in the circulation prior to TBI, the brain would readily access the BCAA and the severity of injury could be reduced. Methods: A standard weight-drop method was used on 50 adult mice to model a closed-head TBI in humans. The mice were randomized into groups that were shams, untreated, and pre-treated with BCAA, post-treated with BCAA, or pre-treated + post-treated with BCAA. Pretreated mice received BCAA through supplemented water and were dosed via oral gavage 45 mins prior to TBI induction. All mice underwent beam walking to assess motor recovery and Morris water maze assessed cognitive function post-injury. Results: Pre-treated and pre-treated + post-treated mice exhibited significantly better motor recovery and cognitive function than the other groups. The pre-treated + post-treated group performed the best overall while the post-treated group only improved in memory after day 7 of the study. Conclusion: This is the first study, animal or human, to demonstrate BCAA are neuroprotective and neurorestorative after TBI, most likely through the important roles of BCAA to glutamate homeostasis.Item Characterization of rHDL Nanoparticles as a Delivery Vehicle for Glioblastoma Multiforme Chemotherapy(2021) Mathew, Ezek; Sabnis, Nirupama; Dossou, Akpedje; Dickerman, Rob; Lacko, Andras G.; Fudala, RafalPurpose: Glioblastoma Multiforme (GBM), is a brain tumor that presents with a very poor prognosis; new approaches are needed to improve patient outcomes. Design of an effective therapeutic approach must include a suitable delivery vehicle, which can cross the blood-brain barrier, and can selectively target GBM tumors. Our project uses reconstituted high-density lipoprotein (rHDL) nanoparticles (NPs), which possess the above characteristics, amplifying efficacy of chemotherapy. To target the PI3K/mTOR pathway involved in the pathophysiology of GBM, we chose to encapsulate PI-103 in preliminary studies. Methods: After encapsulation and purification, the drug-containing rHDL NPs will be characterized with regard to their physical/chemical properties. We will assess drug loading, entrapment efficiency, stability, particle diameter, homogeneity and molecular weight. Afterwards, cytotoxicity against human GBM cells will be compared to normal human astrocytes. Because the scavenger receptor B type 1 (SR-B1) is known to interact with circulating HDL and the rHDL NPs, we will compare the cytotoxic efficiency of the drug transporting rHDL NPs against a high SR-B1 expressing GBM line (LN229) versus a low SR-B1 expressing GBM line (U87MG). SR-B1 levels will be assessed for all cell lines. Results: In this work we will demonstrate that after encapsulation of PI-103 into rHDL and characterization, we will observe cytotoxic effect against GBM cell lines, not normal astrocytes. Conclusion: If successful, future spheroid and mice studies, in addition to combination therapy studies, will advance the proof of concept of this therapy, allowing translation toward clinical applications.Item In-Vitro Assessment of Cortical Repair Induced by Branched-chain Amino Acid Treatment(2024-03-21) Mathew, Ezek; Jones, Nathan; Dickerman, Rob; Ortega, SterlingPurpose: Traumatic Brain Injury (TBI) refers to a constellation of pathologies resulting from mechanical damage to cortical tissue. The neurological sequala of such injuries can be devastating, and definitive treatment does not exist at this time. Branched-chain Amino Acid (BCAA) treatment has demonstrated neuroprotective effects in clinical literature and in various animal models of TBI. However, there is a lack of in-vitro literature referencing the repair capacity of BCAA administration after neuronal injury, particularly in the context of TBI. To fill this gap in knowledge, a scratch assay was repurposed for use in cortical culture, to assess the repair capacity of BCAA treatment. Methods: Mouse-derived Mixed Cortical Culture (MCC) cells were extracted and seeded in 24 well plates. A scratch assay was performed, where a vertical scratch was drawn across each well in a reproducible manner with a 200 uL pipette tip. This procedure is meant to recapitulate aspects of mechanical damage induced by TBI on cortical tissue. Subsequently, images were taken immediately post-injury (0 hour time point), at 24 hour, and at 48 hour time points post-scratch to quantify the area of scratch unfilled by cells. Various dose concentrations of BCAA were tested in comparison to control (media only) and vehicle control (water). Test conditions included the customary BCAA ratio, which is a 2:1:1 mix of leucine, isoleucine, and valine; additionally, a 1:1:1 ratio of leucine, isoleucine, and valine was also tested. Results: At 48 hours post-scratch, significant differences were found in open wound area when comparing the media only control to 10 uM (p < 0.01), 30 uM (p < 0.01), 300 uM (p < 0.001), and 1000 uM (p < 0.01) of the 2:1:1 BCAA dose. Significant differences were also found in the wound area when comparing the water vehicle control to 10 uM (p < 0.05), 30 uM (p < 0.01), 300 uM (p < 0.01), and 1000 uM (p < 0.01) of the 2:1:1 BCAA dose. No significant differences were found in the open wound area when comparing the controls and BCAA doses, at the 24 hour time point. Of note, no significant differences were found between control and treatment with the 1:1:1 ratio of leucine, isoleucine, and valine at any time point. Conclusion: BCAA treatment at the 2:1:1 ratio was seen to accelerate injury recovery at various dose concentrations, as quantified by open wound area after scratch injury was induced. This cell culture model demonstrates the importance of BCAA ratios. While this aligns with animal models and clinical literature, this is the first in-vitro assessment of BCAA repair capacity, in the context of cortical culture. Future studies will be undertaken to further elucidate the constituents of the repair mechanism.Item Left Hemi-Diaphragmatic Paralysis After Left Cervical Transforaminal Epidural Steroid Injection of the C5-C6 Level(2020) Mathew, Ezek; Dickerman, Rob; Farrell, MollyBackground: Cervical radiculopathy is a common cause of neck pain with radiation into the upper extremity in a dermatomal pattern. The age-adjusted incidence is 83.2 per 100,000 persons per year. The most common causes are vertebral spondylosis and intervertebral disc herniation. Corticosteroid injection is a conservative management option with a low risk of major adverse events. Adverse events could include epidural hematoma, infection, allergic reactions, seizures, nerve damage, or intravascular injections. No reviewed literature or case reports have indicated phrenic nerve injury secondary to cervical transforaminal epidural steroid injection (TFESI). Case Presentation: A 45-year-old male physician with severe left C6 radiculopathy secondary to a large left-sided C5-C6 herniated intervertebral disc presented to the neurosurgical clinic. The patient underwent a left side C6 TFESI. Immediately upon awakening from anesthesia, the patient experienced shortness of breath. A Sniff test demonstrated the patient had left diaphragmatic paralysis. Six weeks later, the patient underwent a C5-C6 anterior cervical discectomy and fusion with complete relief of his radicular symptoms. The left hemi-diaphragmatic paralysis remained at the one-year postoperative visit. Conclusion: A thorough literature review shows no indication of phrenic nerve injury with cervical TFESI. In the current study, we explore the suspected mechanisms of possible injury to the phrenic nerve. Epidural corticosteroid injection is a viable and safe option for conservative management of cervical radiculopathy. This report unveils a unique and important adverse event that should be held in consideration before undergoing a cervical TFESI.Item Transverse Myelitis After Johnson & Johnson COVID Vaccine - A Case Report(2022) Mathew, Ezek; Williamson, Julie; Johnson, Reign; Mamo, Lois; Mahama-Rodriguez, Alia; Dickerman, RobIntroduction: As the novel coronavirus disease of 2019 (COVID) is an ongoing public health issue, many turn to vaccinations as a means of defense. While vaccination is generally safe, reports of rare pathologies subsequent to COVID vaccination exist, especially in the realm of neurological disorders. One such rare complication is tranverse myelitis, which will be the subject of this case report. Patients impacted by transverse myelitis may present with a varied neurological symptom, which may sometimes progress rapidly without treatment. These can include motor, sensory, and/or autonomic dysfunctions stemming from the spinal cord. These dysfunctions typically occur bilaterally at clearly defined sensory levels, and T2 weighted MRI will indicate cord hyperintensity. Case Description: A 56-year-old male patient presented to clinic with a chief complaint of episodic bilateral arm numbness. The patient tested positive for COVID in December of 2020, although recovery was uneventful. In May of 2021, the patient received the Johnson & Johnson COVID vaccine. The symptoms associated with his chief complaint developed approximately two months after receiving the vaccine. Two weeks preceding the patient visit, cervical Magnetic Resonance Imaging (MRI) was performed. Imaging evidenced severe cord edema from C1 to T1-2 with associated cord expansion. At C4-C5, there is a right sided disc protrusion causing moderate spinal stenosis with cord effacement. Additionally, the thecal sac measures 7mm at this level. At the C5-C6 and C6-C7 levels, there is evidence of moderate foraminal stenosis, bilaterally. Radiological evaluation confirmed these findings, while listing possible differentials of transverse myelitis, neuromyelitis optica, or a viral myelitis. Along with recommendation for follow up and referral for contrast MRI, oral corticosteroid treatment was rapidly initiated. One week after treatment, another cervical MRI was performed. The radiology interpretation noted decreased extent of the abnormal enhancing signal within the cervical cord, compatible with resolving transverse myelitis. Over the time course of multiple weeks, symptoms improved. Discussion: While the majority of cases may yield abnormal strength and DTR, transverse myelitis presentations after COVID vaccination may ultimately vary widely, necessitating thorough evaluation. The prognosis of transverse myelitis is rather varied and depends on factors such as rate of symptom progression, quality of nerve conduction, possibility of spinal shock, and speed of treatment initiation. Prompt treatment and management of symptoms may allow for a successful recovery, as in this patient's case.Item Unilateral to Bilateral Progressive Sciatic Neuropathy After Radiotherapy: A Case Report(2024-03-21) Mathew, Ezek; Drown, Mariah; Abarquez, Angela; Shivnani, Anand; Ortega, Sterling; Dickerman, RobBackground: Radiation therapy is often an adjunct treatment for prostate cancer. However, this procedure is not without risks; as the lumbosacral plexus is not routinely contoured during radiotherapy treatment plans, this raises potential for unintended consequences. As this case, especially this particular presentation, is an extremely rare occurrence, we will examine relevant literature and discuss the challenging diagnosis. Case Presentation: In this report, we detail the case of a 66-year-old male patient who suffered from unilateral sciatic neuropathy. Unfortunately, this unilateral neuropathy became bilateral, and was deemed idiopathic at the time, causing the patient severe distress. However, further workup which consisted of examination of patient history, scrutinizing imaging, and electromyography (EMG), painted a different picture. The onset of the patient’s complaints appeared to be initiated by adaptive radiotherapy, which the patient underwent during his treatment regimen for prostate cancer. Conclusions: As radiation-induced lumbosacral plexopathy (RILSP) may present in a delayed fashion after treatment, diagnosis could become difficult. While radiculopathy was the differential diagnosis which initially led to neurosurgical consultation, the patient’s presentation did not align with this diagnosis. Further workup, especially strategic usage of EMG, allowed for discernment of a neuropathic condition, versus a mechanically induced radiculopathy. While RILSP appears to be an underreported phenomenon subsequent to pelvic radiation, there exists only one other case of such neuropathy after prostate radiotherapy. Knowledge of this case will enable clinicians to modify their workup and avoid spine surgery in cases where it may cause harm.