Publications by authors named "Tye Patchana"

26 Publications

  • Page 1 of 1

Osteopathic Manipulative Treatment to Optimize the Glymphatic Environment in Severe Traumatic Brain Injury Measured With Optic Nerve Sheath Diameter, Intracranial Pressure Monitoring, and Neurological Pupil Index.

Cureus 2021 Mar 11;13(3):e13823. Epub 2021 Mar 11.

Neurosurgery, Arrowhead Regional Medical Center, Colton, USA.

Background Traumatic brain injury (TBI) has a complex pathophysiology that has historically been poorly understood. New evidence on the pathophysiology, molecular biology, and diagnostic studies involved in TBI have shed new light on optimizing rehabilitation and recovery. The goal of this study was to assess the effect of osteopathic manipulative treatment (OMT) on peripheral and central glial lymphatics in patients with severe TBI, brain edema, and elevated intracranial pressure (ICP) by measuring changes in several parameters regularly used in management. Methodology This was a retrospective study at a level II trauma center that occurred in 2018. The study enrolled patients with TBI, increased ICP, or brain edema who had an external ventricular drain placed. Patients previously underwent a 51-minute treatment with OMT with an established protocol. Patients received 51 minutes of OMT to the head, neck, and peripheral lymphatics. The ICP, cerebrospinal fluid (CSF) drainage, optic nerve sheath diameter (ONSD) measured by ultrasonography, and Neurological Pupil Index (NPi) measured by pupillometer were recorded before, during, and after receiving OMT. Results A total of 11 patients were included in the study, and 21 points of data were collected from the patients meeting inclusion criteria who received OMT. There was a mean decrease in the ONSD of 0.62 mm from 6.24 mm to 5.62 mm (P = 0.0001). The mean increase in NPi was 0.18 (P = 0.01). The mean decrease in ICP was 3.33 mmHg (P= 0.0001). There was a significant decrease in CSF output after treatment (P = 0.0001). Each measurement of ICP, ONSD, and NPi demonstrated a decrease in overall CSF volume and pressure after OMT compared to CSF output and ICP prior to OMT. Conclusions This study demonstrates that OMT may help optimize glial lymphatic clearance of CSF and improve brain edema, interstitial waste product removal, NPi, ICP, CSF volume, and ONSD. A holistic approach including OMT may be considered to enhance management in TBI patients. As TBI is a spectrum of disease, utilizing similar techniques may be considered for all forms of TBI including concussions and other diseases with brain edema. The results of this study can better inform future trials to specifically study the effectiveness of OMT in post-concussive treatment and in those with mild-to-moderate TBI.
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http://dx.doi.org/10.7759/cureus.13823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038899PMC
March 2021

Risk Factors Associated with 90-day Readmissions Following Odontoid Fractures- A Nationwide Readmissions Database Study.

Spine (Phila Pa 1976) 2021 Feb 22. Epub 2021 Feb 22.

Swedish Neuroscience Institute, Swedish Medical Center, Seattle, Washington, United States Seattle Science Foundation, Seattle, Washington, United States Department of Trauma Surgery, BG University Hospital Bergmannsheil, Bochum, Germany Hansjörg Wyss Hip and Pelvic Center, Swedish Medical Center, Seattle, Washington, United States. Division of Neurosurgery, Riverside University Health Systems, Moreno Valley, California, United States. Department of Orthopaedic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Study Design: Nationwide Readmissions Database Study.

Objective: To investigate readmission rates and factors related to readmission after surgical and non-surgical management of odontoid fractures.

Summary Of Background Data: Management of odontoid fractures, which are the most common isolated spine fracture in the elderly, continues to be debated. The choice between surgical or non-surgical treatment has been reported to impact mortality and might influence readmission rates. Hospital readmissions represent a large financial burden upon our healthcare system. Factors surrounding hospital readmissions, would benefit from a better understanding of their associated causes in order to lower health care costs.

Methods: A retrospective study was performed using the 2016 Healthcare Utilization Project (HCUP) Nationwide Readmission Database (NRD). Demographic information and factors associated with readmission were collected. Readmission rates, complications, length of hospital stay were collected. Patients treated operatively, non-operatively, and patients who were readmitted or not readmitted were compared. Statistical analysis was performed using open source software SciPy (Python v1.3.0) for all analyses.

Results: We identified 2,921 patients who presented with Type II dens fractures from January 1st 2016 to September 30th 2016, 555 of which underwent surgical intervention. The readmission rate in patients who underwent surgery was 16.4% (91/555) and 29.4% (696/2366) in the non-operative group. Hospital costs for readmitted and non-readmitted patients were $353,704 and $174,922, and $197,099 and $80,715 for non-operatively managed patients, respectively. Medicaid and Medicare patients had the highest readmission rate in both groups. Charlson and Elixhauser comorbidity indices were significantly higher in patients who were readmitted (p < 0.0001).

Conclusion: We report an overall 90-day readmission rate of 16.4% and 29.4%, in operative and non-operative management of type II odontoid fractures, respectively. In the face of a rising incidence of this fracture in the elderly population, an understanding of the comorbidities and age-related demographics associated with 90-day readmissions following both surgical and non-surgical treatment are critical.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000004010DOI Listing
February 2021

Inflammatory Markers in Severity of Intracerebral Hemorrhage II: A Follow Up Study.

Cureus 2021 Jan 10;13(1):e12605. Epub 2021 Jan 10.

Neurosurgery, Arrowhead Regional Medical Center, Colton, USA.

Introduction Spontaneous intracerebral hemorrhage (ICH) results in significant morbidity and mortality. The pathogenesis of brain injury after ICH is thought to be due to mechanical damage followed by ischemic, cytotoxic, and inflammatory changes in the underlying and surrounding tissue. Various inflammatory and non-inflammatory biomarkers have been studied as predictors and potential therapeutic targets for intracerebral hemorrhage. Our prior study showed an association with low vascular endothelial growth factor (VEGF) levels and increased mortality. This current study looks to expand on our prior results and will look at the relationship between tumor necrosis factor alpha (TNFα), C-reactive protein (CRP), VEGF, Homocysteine (Hcy), and CRP to albumin ratio (CAR) in predicting outcomes and severity in spontaneous intracerebral hemorrhage. Methods We conducted a retrospective chart review of patients with spontaneous intracerebral hemorrhage with TNFα, CRP, VEGF, Hcy levels drawn on admission. Albumin and CRP levels on admission were used to calculate CAR. Ninety-nine patients were included in the study. Primary outcomes included death, early neurologic decline (END), and hemorrhage size. Secondary outcomes included late neurologic decline (LND), Glasgow Coma Scale (GCS) on admission, GCS on discharge, ICH score, change in hemorrhage size, need for surgical intervention, and length of ICU stay. Results A total of 99 patients were included in this study, with 42% requiring surgical intervention and an overall mortality of 16%. Basal ganglia hemorrhage was seen in 41% of patients. Hcy and CAR were significantly correlated with ICH size in basal ganglia patients (r-=0.36, p=0.03; r=0.43, p=0.03, respectively). CAR was significantly correlated with ICH score (r=0.33, p=0.007874). Admission VEGF levels less than 45 pg/ml had 8.4-fold increase in mortality (odds ratio [OR] 8.4545, p=0.0488). Patients with TNFα levels greater than 1.40 pg/ml had a 4.1-fold increase in mortality (OR 4.1, p=0.04) Conclusion Our study demonstrated that low levels (<45 pg/ml) of VEGF were associated with an 8.4-fold increase in mortality, supporting the neuroprotective effect of this protein. Elevated Hcy and CAR levels were associated with an increase in hemorrhage size in patients with basal ganglia hemorrhages. TNFα levels greater than 1.40 pg/ml were associated with a 4.1-fold increase in mortality, and this together with CAR being correlated with increased hemorrhage size and ICH score further demonstrate the inflammatory consequences after intracerebral hemorrhage. Future studies directed at lowering CRP, TNFα, and Hcy and/or increasing VEGF in intracerebral hemorrhage patients are needed and may be beneficial.
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http://dx.doi.org/10.7759/cureus.12605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872478PMC
January 2021

Retraction: Racial Disparity Amongst Stroke Patients During the Coronavirus Disease 2019 Pandemic.

Cureus 2021 Jan 13;13(1):r21. Epub 2021 Jan 13.

Neurosurgery, Arrowhead Regional Medical Center, Colton, USA.

[This retracts the article DOI: 10.7759/cureus.10369.].
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http://dx.doi.org/10.7759/cureus.r21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806224PMC
January 2021

Timing of Chemoradiation in Newly Diagnosed Glioblastoma: Comparative Analysis Between County and Managed Care Health Care Models.

World Neurosurg 2021 Jan 19. Epub 2021 Jan 19.

Department of Neurological Surgery, Riverside University Health System, Moreno Valley, California, USA; Department of Neurological Surgery, Arrowhead Regional Medical Center, Colton, California, USA.

Background: Glioblastoma multiforme (GBM) is a primary brain malignancy with significant morbidity and mortality. The current standard of treatment for GBM is surgery followed by radiotherapy and temozolomide. Despite an established treatment protocol, there exists heterogeneity in outcomes due to patients not receiving all treatments. We analyzed patients in different health care models to investigate this heterogeneity.

Methods: A retrospective analysis was performed at 2 hospitals in San Bernardino County, California, for patients with newly diagnosed GBM from 2004 to 2019. Patients younger than 18 years of age, with history of low-grade glioma, who had undergone prior treatment, and those lost to follow-up were excluded.

Results: A total of 57 patients were included in our study. Chemotherapy was started at 41 ± 30 and 77 ± 68 days in the health maintenance organization (HMO) and county model, respectively (P = 0.050); radiation therapy was started at 46 ± 34 and 85 ± 76 days in the HMO and county models, respectively (P = 0.036). In individuals who underwent both chemotherapy and radiation therapy (XRT), the difference in time to XRT was no longer significant (P = 0.060). Recurrence time was 309 ± 263 and 212 ± 180 days in the HMO and county groups, respectively (P = 0.379). The time to death was 412 ± 285 and 343 ± 304 days for HMO and county models, respectively (P = 0.334).

Conclusions: Our study demonstrates a statistically significant difference in time to adjuvant therapies between patients within a county hospital and a managed health care organization. This information has the potential to inform future policies and care coordination for patients within the county model.
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http://dx.doi.org/10.1016/j.wneu.2021.01.023DOI Listing
January 2021

Use of Endovascular Simulator in Training of Neurosurgery Residents - A Review and Single Institution Experience.

Cureus 2020 Dec 6;12(12):e11931. Epub 2020 Dec 6.

Neurosurgery, Arrowhead Regional Medical Center, Colton, USA.

Simulators for surgical procedures and interventions have undergone significant technological advancement in the past decade and are becoming more commonplace in medical training. Neurosurgery residents across multiple training levels underwent performance evaluation using a neuro-interventional simulator, employing a variety of metrics for assessment. We identified seven core metrics used in the evaluation of neurosurgery residents performing simulated mechanical thrombectomies. Additionally, a systematic PubMed search for studies related to Neurointerventional Radiology training via simulation was performed. The purpose of this study is to examine the validity and benefits of training with these simulation devices and compare our institution's experience. Additionally, an exploration of their applicability to neurosurgery resident training is discussed.
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http://dx.doi.org/10.7759/cureus.11931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785465PMC
December 2020

Spinal Arteriovenous Malformation: Case Report and Review of the Literature.

Cureus 2020 Nov 21;12(11):e11614. Epub 2020 Nov 21.

Neurosurgery, Desert Regional Medical Center, Palm Springs, USA.

Spinal arteriovenous malformations (AVMs) are a rare form of spinal blood vessel defect that results in vessel engorgement leading to clinical signs secondary to mass effect and ischemia. We present the patient's clinical course following suspicion of spinal AVM along with a review of current classification and imaging modalities.
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http://dx.doi.org/10.7759/cureus.11614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752798PMC
November 2020

Generalized Dystonia Treated With Deep Brain Stimulator: An Institutional Single Surgeon Experience.

Cureus 2020 Oct 16;12(10):e10992. Epub 2020 Oct 16.

Neurosurgery, Kaiser Permanente, Los Angeles, USA.

Introduction Dystonia can cause severe disability when left untreated. Once a patient has exhausted medical management, surgical intervention may be the only treatment option. Although not curative, deep brain stimulation has been shown to be beneficial for patients affected by this condition. Our study sought to review patients undergoing deep brain stimulation for medically refractory dystonia to assess outcomes. Methods Our institution's operative database was reviewed retrospectively for all patients undergoing deep brain stimulator placement over the last six years. These medical records were reviewed for the severity of dystonia preoperatively and followed postoperatively for 24 months, focusing on the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Patients with less than two-year postoperative follow-up were excluded from the study. The patients were further stratified by age into Group A, consisting of patients less than 40 years old, and Group B, patients greater than or equal to 40 years old. Other attributes such as age, sex, age of disease onset, disease duration at the time of surgery, genetic tests for dystonia-related genes, and any complication associated with surgery were also reviewed. Results Four hundred fifty-five operative cases for deep brain stimulator placement were reviewed, and 16 patients met inclusion criteria for the study. The mean age for our patient cohort was 43.75 years, with four males and 12 females. The average time from the age of disease onset to time of surgery was 9.7 years for Group A and 10.8 years for Group B; the overall average was 10.3 years. All patients had globus pallidus interna (GPi) as their surgical target. The first incidence of a statistically significant decrease in BFMDRS score was noted at three months postoperatively (p<0.001) when compared to preoperative values. Fourteen patients in our cohort underwent preoperative genetic testing for DYT gene mutations, out of which four were found to have a mutation. Conclusion Our review of outcomes for primary generalized dystonia at our institution found that deep brain stimulator targeting the GPi is safe and effective. We found an overall 88% response rate with younger patients (< 40-year-old) showing a better response at two years than older patients.
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http://dx.doi.org/10.7759/cureus.10992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668228PMC
October 2020

Racial Disparity Amongst Stroke Patients During the Coronavirus Disease 2019 Pandemic.

Cureus 2020 Sep 10;12(9):e10369. Epub 2020 Sep 10.

Neurosurgery, Arrowhead Regional Medical Center, Colton, USA.

Introduction The global coronavirus disease 2019 (COVID-19) pandemic has had deleterious effects on our healthcare system. Lockdown measures have decreased the number of patients presenting to the hospital for non-respiratory illnesses, such as strokes. Moreover, there appears to be a racial disparity among those afflicted with the virus. We sought to assess whether this disparity also existed for patients presenting with strokes. Methods The Get with the Guidelines National Stroke Database was reviewed to assess patients presenting with a final diagnosis of ischemic stroke, transient ischemic attack (TIA), subarachnoid hemorrhage (SAH), or spontaneous/nontraumatic intraparenchymal hemorrhage (IPH). The period of February - May 2020 was chosen given the surge of patients affected with the virus and national shutdowns. Data from this same time during 2019 was used as the control population. Our hospital numbers and four additional regions were assessed (California hospitals, Pacific State hospitals, Western Region hospitals, and all hospitals in the United States). Patients were categorized by race (White, Black/African American, Asian, Native American, Hispanic) in each cohort. The primary endpoint of this study is to compare whether there was a significant difference in the proportion of patients in each reported racial category presenting with stroke during the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results A downward trend in total number of patients was noted in all five regional cohorts assessed. A statistically significant increase in the number of Black and Hispanic patients presenting with strokes was noted in California, Pacific hospitals, Western hospitals, and all hospitals in the United States during various months studied comparing 2020 to 2019. A statistically significant increase in the Hispanic population was noted in February and March in all California hospitals (p=0.005 and 0.02, respectively) and Pacific Coast hospitals (p=0.005 and 0.039, respectively). The Western region and all national hospitals noted a significant increase in strokes in the Hispanic population in April (p=0.039 and 0.023, respectively). A statistically significant increase of strokes in the Black population was noted in April in Pacific hospitals, Western region hospitals, and all national hospitals (p=0.039, 0.03, and 0.03, respectively). Conclusion The COVID-19 pandemic has adversely affected certain racial groups more than others. A similar increase is noted in patients presenting with strokes in these specific racial populations. Moreover, lack of testing for the SARS-CoV-2 virus may be missing a possible link between racial disparity for patients infected with the virus and patients presenting with stroke. The authors advocate for widespread testing for all patients to further assess this correlation.
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http://dx.doi.org/10.7759/cureus.10369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549889PMC
September 2020

Optimal Partial Pressure of Oxygen Affects Outcomes in Patients With Severe Traumatic Brain Injury.

Cureus 2020 Aug 23;12(8):e9964. Epub 2020 Aug 23.

Neurosurgery, Arrowhead Regional Medical Center, Colton, USA.

Introduction Severe traumatic brain injury (TBI) is a leading cause of death and disability. Not all neuronal damage occurs at the time of primary injury, but rather TBI initiates a cascade of events that leads to secondary brain injury. Oxygenation is one crucial factor in maintaining brain tissue homeostasis post-injury. We performed a retrospective review of patients admitted to a single trauma center after TBI. Statistical analysis was performed to ascertain if the measured partial pressure of oxygen (PaO₂) affected overall outcome at the time of discharge from the hospital. Materials and Methods Statistical analysis was performed retrospectively on patients admitted with a Glasgow Coma Scale (GCS) < 8 and a diagnosis of TBI. GCS and Glasgow Outcome Scale (GOS) were calculated from physical examination findings at the time of hospital discharge or death. Patient data were separated into two groups: those with consistently higher average PaO₂ scores (≥ 150 mmHg; n = 7) and those with lower average PaO₂ scores (< 150 mmHg; n = 8). The minimum requirement to be categorized in the consistently higher group was to have an average hospital day 1 through 5 PaO₂ value of ≥ 150 mmHg. Results Patients with consistent hospital Day 1 through 5 PaO₂ scores of ≥ 150 mmHg had statistically significant higher GCS scores at the end of intensive care unit (ICU)-level care or hospital discharge (mean = 12, = 0.01), compared to those in group 2 with lower PaO₂ levels (mean = 7.9). There was no statistically significant difference in GOS when comparing the two groups ( = 0.055); however, the data did show a trend toward significance. Discussion and Conclusion In our study we analyzed patients diagnosed with TBI and stratified them into groups based on PaO₂ ≥ or < 150 mmHg. We demonstrate overall outcome improvement based on GCS with a trend toward improved GOS. The GCS showed statistical significance in patients with PaO₂ consistently ≥ 150 mmHg versus those in group 2 over the first five days of hospitalization.
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http://dx.doi.org/10.7759/cureus.9964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510506PMC
August 2020

Subgaleal hematoma evacuation in a pediatric patient: A case report and review of the literature.

Surg Neurol Int 2020 15;11:243. Epub 2020 Aug 15.

Department of Neurosurgery, Kaiser Permanente, Fontana, California, United States.

Background: Subgaleal hematoma (SGH) is generally documented within the neonatal period and is rarely reported as a result of trauma or hair braiding in children. While rare, complications of SGH can result in ophthalmoplegia, proptosis, visual deficit, and corneal ulceration secondary to hematoma extension into the orbit. Although conservative treatment is preferential, expanding SGH should be aspirated to reduce complications associated with further expansion.

Case Description: A 12-year-old African-American female with no recent history of trauma presented with a chief complaint of headache along with a 2-day history of enlarging 2-3 cm ballotable bilateral frontal mass. Hematological workup was negative. The patient's family confirmed a long history of hair braiding. The patient was initially prescribed a period of observation but returned 1-week later with enlarging SGH, necessitating surgical aspiration.

Conclusion: SGH is rare past the neonatal period, but can be found in pediatric and adolescent patients secondary to trauma or hair pulling. Standard workup includes evaluation of the patient's hematological profile for bleeding or coagulation deficits, as well as evaluation for child abuse. Although most cases of SGH resolve spontaneously over the course of several weeks, close follow-up is recommended. The authors present a case of a 12-year-old female presenting with enlarging subgaleal hemorrhages who underwent surgical aspiration and drainage without recurrence. A literature review was also conducted with 32 pediatric cases identified, 20 of which were related to hair pulling, combing, or braiding. We review the clinical course, imaging characteristics, surgical management, as well as a review of the literature involving subgaleal hemorrhage in pediatric patients and hair pulling.
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http://dx.doi.org/10.25259/SNI_207_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468241PMC
August 2020

Spontaneous Spinal Subdural Hematoma Mimicking Myocardial Infarction.

Cureus 2020 Jul 30;12(7):e9486. Epub 2020 Jul 30.

Neurosurgery, Wellington Regional Medical Center, Wellington, USA.

Spontaneous spinal subdural hematomas (SSDHs) are rarely encountered in clinical practice. In this paper, we report a case of a 70-year-old female who presented to the Emergency Department with symptoms of mid-epigastric pain radiating to her mid-scapular region. Her workup demonstrated mildly elevated cardiac troponin I levels and electrocardiogram (ECG) leads V3-V5 ST-depressions. She was subsequently treated through the non-ST elevation myocardial infarction (NSTEMI) protocol and given an antiplatelet agent. The next morning, she developed bilateral lower extremity paresthesias, progressive left lower extremity weakness, and urinary retention. Magnetic resonance imaging (MRI) of the spine demonstrated a hematoma in the thoracic region resulting in spinal cord compression. The patient underwent surgical decompression. After the decompression of the thoracic spinal cord, the patient's neurological symptoms gradually improved and she regained lower extremity function. This report brings to light a very unusual presentation of an uncommon clinical entity. To the best knowledge of the authors, spontaneous SSDH presenting as myocardial injury and subsequently exacerbated by anticoagulation therapy has not been reported in the literature to date.
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http://dx.doi.org/10.7759/cureus.9486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455467PMC
July 2020

Case Report: Projectile Into Right Frontal Lobe From a Nail Gun.

Cureus 2020 Jul 29;12(7):e9460. Epub 2020 Jul 29.

Neurosurgery, Arrowhead Regional Medical Center, Colton, USA.

We present a case of a nail gun injury penetrating the right maxillary sinus and frontal lobe with complaints of headache and right eye blindness. After surgical removal and treatment, there were no neurological deficits aside from the persistence of right eye blindness that the patient initially presented with. Our report describes the patient's clinical course, the multidisciplinary medical and surgical management, along with the clinical workup and important mental health considerations for patients presenting with intracranial nail gun injuries.
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http://dx.doi.org/10.7759/cureus.9460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455395PMC
July 2020

Pediatric sellar solitary fibrous tumor/ hemangiopericytoma: A rare case report and review of the literature.

Surg Neurol Int 2020 8;11:238. Epub 2020 Aug 8.

Department of Neurosurgery, Kaiser Permanente, Fontana, California, United States.

Background: Solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) is a rare tumor which originates from the walls of capillaries and has historically been thought to be able to occur anywhere in the body that blood vessels are found. It is rarely found in the sellar region.

Case Description: InS this report, we present the first case of this tumor occurring in the sellar region of a pediatric patient. This 12-year-old male presented with progressive vision loss which prompted surgical resection after a sellar lesion was discovered on imaging. The initial transsphenoidal approach resulted in subtotal resection and the patient experienced reoccurrence within 3 months. He underwent an orbitozygomatic craniotomy to achieve gross total tumor resection.

Conclusion: We conducted a literature review of intracranial SFT/HPC in the pediatric population and found it to be an extremely rare occurrence, with <30 cases reported. The incidence of SFT/HPC occurring in the sellar region for any age group was also found to be a rare entity. Treatment recommendations for this tumor are also scarce, based on retrospective chart reviews from the adult population. The role for adjuvant radiation has mixed results.
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http://dx.doi.org/10.25259/SNI_234_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451149PMC
August 2020

Acquired Holmes Tremor in a Human Immunodeficiency Virus Immune Reconstitution Inflammatory Syndrome Patient Treated with Deep Brain Stimulation.

World Neurosurg 2020 09 19;141:253-259. Epub 2020 Jun 19.

Kaiser Permanente Los Angeles Medical Center, Department of Neurosurgery, Los Angeles, California, USA.

Background: The authors present a case of a 66-year-old male who was diagnosed with human immunodeficiency virus, and his medical course of highly active antiretroviral therapy was complicated with the development of immune reconstitution inflammatory syndrome, which led to development of movement disorder consisting of right-sided resting tremor, neck dystonia, and jaw clenching.

Case Description: The patient's symptoms resembled that of rubral tremor, and he underwent placement of a deep brain stimulation electrode into the left ventral intermediate nucleus of the thalamus with significant improvement of symptoms.

Conclusions: This is the first reported case in the literature of a human immunodeficiency virus-positive patient's treatment course complicated with immune reconstitution inflammatory syndrome with neurologic manifestation, which was refractory to medical therapy and thus treated with deep brain stimulation.
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http://dx.doi.org/10.1016/j.wneu.2020.06.099DOI Listing
September 2020

A Novel Method for Practicing Fascial Closure with Suture.

Cureus 2020 Apr 23;12(4):e7803. Epub 2020 Apr 23.

Neurosurgery, Aurora Medical Center, Summit, USA.

Closure of the fascial layer can be challenging to learn for junior level residents. Wound dehiscence involving the fascial layer can lead to complicated clinical courses for patients, including readmission to the hospital, wound vacuum placement, antibiotic regimens, and re-operation. Typical suturing techniques taught in medical school focus more on basic techniques of suture placement such as interrupted or running techniques. The aim of this study is to introduce a method of practicing fascial closure using easily obtainable items. Though there is no substitute for placement of suture and closure of fascia in vivo, this method allows one to practice the motor repetition of fascial suture placement and provides one with the ability to check their work.
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http://dx.doi.org/10.7759/cureus.7803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243843PMC
April 2020

Metastatic Acetabular Fracture: A Rare Disease Presentation of Recurrent Head and Neck Paraganglioma.

Cureus 2020 Apr 9;12(4):e7596. Epub 2020 Apr 9.

Pathology, Riverside University Health System Medical Center, Moreno Valley, USA.

We present a case of a rare metastatic bone lesion of the acetabulum, associated with a pathologic fracture, found to be metastasis from a malignant carotid body paraganglioma upon histological analysis. We present a report of the patient's clinical course following the identification of metastatic disease to the right acetabulum, as well as a review of paragangliomas and their propensity for metastasis.
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http://dx.doi.org/10.7759/cureus.7596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212738PMC
April 2020

Increased Brain Tissue Oxygen Monitoring Threshold to Improve Hospital Course in Traumatic Brain Injury Patients.

Cureus 2020 Feb 27;12(2):e7115. Epub 2020 Feb 27.

Neurosurgery, Riverside University Health System Medical Center, Moreno Valley, USA.

Introduction This article is a retrospective analysis of the neurosurgical census at our institution to determine an optimal threshold for brain tissue oxygenation (PbtO2). The use of brain tissue oxygen monitoring has been in place for approximately three decades but data suggesting optimal thresholds to improve outcomes have been lacking. Though there are multiple modalities to monitor cerebral oxygenation, the monitoring of brain tissue oxygen tension has been deemed the gold standard. Still, it is not clear exactly how reductions in PbtO2 should be treated or what appropriate thresholds to treat might be. The aim of our study was to determine if our threshold of 28 mmHg for a good functional outcome could be correlated to the Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS). Methods A retrospective analysis of the Arrowhead Regional Medical Center (ARMC) Neurosurgery Census was performed. Patients from 2017-2019 who had placement of Licox® cerebral oxygen monitoring sensors (Integra® Lifesciences, Plainsboro Township, New Jersey) were included in the analysis. Fifteen patients were consecutively identified, all of which presented with traumatic brain injury (TBI). Data on age, gender, days in the intensive care unit (ICU), days before discharge or end of medical care, admission GCS, hospital length of stay, GOS, maximum and minimum PbtO2 values for five days following insertion, minimum and maximum intracranial pressures (ICPs), and brain temperature were included for analysis. Patient data were separated into two groups; those with consistently higher PbtO2 scores (≥ 28 mmHg; n = 7) and those with inconsistent/lower PbtO2 scores (< 28 mmHg; n = 8). Standard student t-tests were used to find potential statistical differences between the groups (α = 0.05). Results There were seven patients in the consistently high PbtO2 category (≥ 28 mmHg) and eight patients in the inconsistent/low PbtO2 category (<28 mmHg). The average maximum and minimum PbtO2 for the group displaying worse outcomes (as defined by GCS/GOS) was 23.0 mmHg and 14 mmHg, respectively. Those with consistent Day 2 PbtO2 scores of ≥ 28 mmHg had significantly higher GCS scores at discharge/end of medical care (p < 0.05). Average GCS for the patient group with >28 mmHg PbtO2 averaged over Days 2-5 group was 11.4 (n=7). Average GCS for the <28 group was 7.0 (n=8). The GCS for the >28 group was 63% higher than found in the <28 group (p = 0.03). GOS scores were significantly higher in those with consistently higher PbtO2 (≥ 28) than those with lower PbtO2 scores (< 28). The averages were 3.5 in the higher PbtO2 group as compared to 2 in the lower PbtO2 group. Conclusion Along with ICP monitors and monitoring in the assessment of CPP, brain tissue oxygenation allows yet another metric by which to optimize treatment in TBI patients. At our institution, a PbtO2 level of ≥ 28 mmHg is targeted in order to facilitate a good functional outcome in TBI patients. Keeping patients at this level improves GCS and GOS at discharge/end of medical treatment.
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http://dx.doi.org/10.7759/cureus.7115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101240PMC
February 2020

Intracatheter Tissue Plasminogen Activator for Chronic Subdural Hematomas after Failed Bedside Twist Drill Craniostomy: A Retrospective Review.

Cureus 2019 Dec 26;11(12):e6472. Epub 2019 Dec 26.

Neurosurgery, Arrowhead Regional Medical Center, Colton, USA.

Introduction Chronic subdural hematomas (cSDH) are common in neurosurgery with various symptoms and significant morbidity and mortality. Treatment varies with procedures including twist-drill (TD) craniostomy, craniotomy, burr hole craniostomy, and craniectomy. Newer treatments including middle meningeal artery embolization are also being explored as no treatment has been determined to be optimal. Due to the lack of consensus treatment, tissue plasminogen activator (tPA) has begun to be investigated to promote drainage and has shown promise in some early studies in reducing recurrence rates. We retrospectively reviewed patients who underwent TD craniostomy and received intracatheter tPA to evaluate the safety and efficacy of this practice. Methods  A single-center retrospective review from December 2018 through August 2018 occurred for patients with cSDH 18 years of age or older who underwent a bedside TD craniostomy. Inclusion criteria included all patients who underwent treatment with TD craniostomy for drainage of cSDH during the time period in which tPA protocol was adopted as a possible therapeutic measure at our center. Exclusion criteria included all patients less than age 18 or incarcerated. Patients were stratified into two groups those that received tPA per our center's neurosurgical protocol and those that received drainage alone. Data collected included demographics, hospital/intensive care unit (ICU) length of stay, operative intervention, cSDH thickness throughout stay, length of drainage, and Glasgow Coma Scale (GCS) on arrival and discharge with analysis performed using -tests. Results In all, 20 patients met inclusion: six received tPA at 48 hours per the institutional neurosurgical protocol and 14 did not. The average thickness of cSDH on arrival was significantly larger in the tPA group (26.5 mm vs 14.46 mm, = 0.0029). Arrival and discharge GCS, average daily drainage, length of stay parameters, and percent change in thickness did not differ between tPA and no tPA groups. The average daily drainage was significantly less prior to the administration of tPA in the tPA group than in the cohort of not receiving tPA (30.71 mL vs 68.99 mL; = 0.011). Average drainage in patients who received tPA after administration was significantly higher compared to pre-tPA values (131.39 mL vs 30.71 mL; = 0.046). No patients were readmitted for re-accumulation or required an operating room procedure. There were no adverse outcomes identified through the instillation of tPA. Conclusion Intracatheter tPA increased drainage rates in the assessment of pre- and post-tPA values when administered at 48 hours after subdural drain (SDD) placement. Patients who received benefits from tPA tended to have larger subdural hematomas and less drainage prior to the instillation of tPA than patients that benefited from drainage alone. Larger prospective studies should investigate early treatment with tPA to identify if tPA is efficacious for all patients after TD craniostomy and to optimize patient selection with regard to thrombolytic therapy.
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http://dx.doi.org/10.7759/cureus.6472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984181PMC
December 2019

Risks, Benefits, and the Optimal Time to Resume Deep Vein Thrombosis Prophylaxis in Patients with Intracranial Hemorrhage.

Cureus 2019 Oct 2;11(10):e5827. Epub 2019 Oct 2.

Neurosurgery, Riverside University Health System Medical Center, Moreno Valley, USA.

Introduction It is common to start all patients on chemical prophylaxis for deep vein thrombosis (DVT) in order to decrease the risk of venous thromboembolism (VTE) and the associated adverse effects, including the potential for fatal pulmonary embolism (PE). There is no consensus in the literature on the optimal time to resume chemical DVT prophylaxis in patients who present with intracranial hemorrhage requiring neurosurgical intervention. The practice is variable and practitioner dependent. There can be difficulty in balancing the increased risk of further intracranial hemorrhage versus the benefit of starting DVT prophylaxis to prevent VTE. Method A retrospective review of patients that had diagnosis of intracranial hemorrhage (ICH) defined as epidural hematoma (EDH), subdural hematoma (SDH), or intra-parenchymal hematoma (IPH), was performed using the neurosurgical census at our institution. The review consisted of adult patients greater than 18 years old with a diagnosis of intracranial hemorrhage. Type of intracranial hemorrhage, method of neurosurgical intervention (whether surgical, bedside procedure, or both), day post-procedure prophylaxis was resumed, and the type of chemical prophylaxis used (subcutaneous heparin (SQH) versus enoxaparin) were recorded. The patient's sex, Glasgow Coma Scale on presentation and discharge, length of hospital stay, and length of intensive care unit (ICU) stay were also recorded. Patients with previously diagnosed bleeding dyscrasia, previously diagnosed DVT or PE, patients without post-procedure cranial imaging (CT or MRI), and patients without post-procedure duplex ultrasound for DVT screening were excluded. Patients were monitored with head CT for possible expansion of ICH after resumption of therapy. Furthermore, we investigated whether the patient developed an adverse effect such as venous thromboembolism including deep vein thrombosis and/or pulmonary embolism during the post-procedure period when they were not on chemical prophylaxis. Results A total of 94 patients were analyzed in our study. Nine (9.6%) had an EDH, seventeen (18.1%) had an IPH, and sixty-eight (72.3%) had a SDH. The three most common procedures were craniectomy (28.7%), craniotomy (34%), and subdural drain placement (28.7%). The most common agent for chemical DVT prophylaxis was SQH in 78% of patients. There was no statistically significant association between type of chemical DVT prophylaxis used with respect to either ICU length of stay or hospital length of stay. Change in GCS (the difference of GCS on presentation versus on discharge) was found to have statistically significant relationship with the use of chemical DVT prophylaxis. Furthermore, patients were found to have no statistically significant association with re-bleed or new hemorrhage upon starting chemical DVT prophylaxis, regardless of the type of ICH. Conclusion The rates of DVT diagnosis did not seem to be significantly affected by the specific type of chemical prophylaxis that was used. ICU and hospital length of stay were not adversely affected by starting prophylaxis for VTE in patients with ICH. On the contrary, an improvement in GCS (on presentation versus discharge) was associated with starting chemical DVT prophylaxis in ICH patients within 24 hours post-procedure.
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http://dx.doi.org/10.7759/cureus.5827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827698PMC
October 2019

Seizure Prophylaxis in Traumatic Brain Injury: A Comparative Study of Levetiracetam and Phenytoin Cerebrospinal Fluid Levels in Trauma Patients with Signs of Increased Intracranial Pressure Requiring Ventriculostomy.

Cureus 2019 Sep 27;11(9):e5784. Epub 2019 Sep 27.

Neurosurgery, Riverside University Health System Medical Center, Moreno Valley, USA.

Background One of the most common life-threatening injuries to trauma patients arriving in the emergency department (ED) is traumatic brain injury (TBI). Traditionally, intravenous medications have been given as seizure prophylaxis in patients demonstrating signs of increased intracranial pressure (ICP), as post-traumatic seizures in trauma patients are associated with higher morbidity and mortality. Medications traditionally given for this indication such as phenytoin have been established to reach therapeutic levels in the cerebrospinal fluid (CSF) quickly and are effective in preventing post-traumatic seizures but often have a large side-effect profile. A newer medication that is being used for seizure prophylaxis in patients with epilepsy is levetiracetam. Levetiracetam typically has a better side effect profile, but it has not been demonstrated that the drug reaches therapeutic levels in the CSF as quickly as phenytoin. Studies have shown levetiracetam and phenytoin to be equivocal in the prevention of post-TBI seizure prophylaxis. Methods This was a prospective, randomized, case-control study at a Level II trauma center of adult patients (age >/= 18 years) who suffered severe TBI (sTBI) requiring the placement of an external ventricular drain (EVD) from May 2017 to June 2018. Twelve patients were randomly placed into one of two groups for the administration of antiepileptic medication (either levetiracetam or phenytoin), allowing for the subsequent serial collection of CSF for the analysis of therapeutic levels of antiepileptic medications. Levetiracetam or phenytoin was administered at standardized fixed doses per our neurosurgical center standard protocol. CSF was collected before either drug was administered, 60 minutes after completion of administration and 360 minutes after completion of drug administration. Data analysis was performed to compare the time frame for which therapeutic levels of the medications were achieved in the CSF. The published steady-state and therapeutic CSF level of levetiracetam is 32 mcg/ml and phenytoin is 2 mcg/ml. Results A trend was observed in which the closer the fixed dosage approximated the weight-based dosing of phenytoin, the more their CSF phenytoin level increased (and approximated the therapeutic range) with an associated R-squared value of 0.6274. This trend was not found in patients receiving levetiracetam. Conclusions Levetiracetam does not reach levels needed for seizure prophylaxis in human CSF when loaded at standard dosing regimens in the acute setting. Phenytoin does reach levels needed for seizure prophylaxis in human CSF with standardized regimen dosing when dosages approximate weight-based dosing. If needed, in the acute setting phenytoin should have additional doses given prior to six hours after the loading dose to achieve therapeutic CSF levels.
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http://dx.doi.org/10.7759/cureus.5784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825487PMC
September 2019

Impressions of Osteopathic Neurosurgeon on Preparedness for Practice: Survey Results from the American College of Osteopathic Surgeons.

Cureus 2019 Sep 25;11(9):e5757. Epub 2019 Sep 25.

Neurosurgery, Riverside University Health System Medical Center, Moreno Valley, USA.

Introduction Neurosurgeons trained in the US are rigorously educated on the surgical management of neurosurgical conditions. These neurosurgeons have been trained through one of two avenues: the Accreditation Council for Graduate Medical Education (ACGME) or the American Osteopathic Association (AOA). With the formation of a single accreditation system from the AOA and ACGME accrediting bodies and significant changes introduced in the training of neurosurgeons from both bodies, we sought to identify common practice parameters and perceptions of preparedness of AOA-trained neurosurgeons. Methods  A survey was conducted through the neurosurgery section of the American College of Osteopathic Surgeons (ACOS), requesting responses from attending neurosurgeons who completed AOA neurosurgery residency. Responses were obtained through an anonymous, web-based system using single-select multiple-choice questions. Results  In total, 52 neurosurgeons participated in the survey. The majority of the 52 respondents practiced in non-academic settings in urban areas and were exposed to a wide variety of practice environments in terms of case volume and clinical responsibilities. Significantly, 96.15% of the respondents said they felt adequately prepared for neurosurgical practice after their AOA training.  Conclusion  Overall, this study highlights both the similarities and variances in practices of osteopathic neurosurgeons. The majority of the participants feel that their training has appropriately prepared them for practice and they are skilled surgeons capable of caring for the safety and well-being of numerous patients in a variety of settings. Most of them practice primarily in private-practice settings at urban centers. Overall, osteopathic neurosurgeons trained in AOA programs report that their training has equipped them well for careers in neurosurgery.
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http://dx.doi.org/10.7759/cureus.5757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825463PMC
September 2019

Prevalence of Catheter-Associated Urinary Tract Infections in Neurosurgical Intensive Care Patients - The Overdiagnosis of Urinary Tract Infections.

Cureus 2019 Aug 26;11(8):e5494. Epub 2019 Aug 26.

Infectious Disease, Arrowhead Regional Medical Center, Colton, USA.

Background: Hospital-acquired infections (HAIs) are profound causes of prolonged hospital stay and worse patient outcomes. HAIs pose serious risks, particularly in neurosurgical patients in the intensive care unit, as these patients are seldom able to express symptoms of infection, with only elevated temperatures as the initial symptom. Data from Center for Disease Control (CDC) and the Infectious Disease Society of America (IDSA) have shown that of all HAIs, urinary tract infections (UTIs) have been grossly over-reported, resulting in excessive and unnecessary antibiotic usage.

Methods: We conducted a retrospective analysis of 686 adult patients that were evaluated by the neurosurgery service at Arrowhead Regional Medical Center between July 2018 and March 2019. Inclusion criteria were adults greater than 18 years of age with neurosurgical pathology requiring a minimum of one full day admission to the intensive care unit (ICU), and an indwelling urinary catheter. Exclusion criteria were patients under the age of 18, those who did not spend any time in the ICU, or with renal pathologies such as renal failure.

Results: We reviewed 686 patients from the neurosurgical census. In total, 146 adult patients with indwelling urinary catheters were selected into the statistical analysis. Most individuals spent an average of 8.91 ± 9.70 days in the ICU and had an indwelling catheter for approximately 8.14 ± 7.95 days. Forty-two out of the 146 individuals were found to have a temperature of 100.4°F or higher. Majority of the patients with an elevated temperature had an infectious source other than urine, such as sputum (22 out of 42, 52.38%), blood (three out of 42, 7.14%) or CSF (one out of 42, 2.38%). We were able to find only two individuals (4.76%) with a positive urine culture and no evidence of other positive cultures or deep vein thrombosis.

Conclusions: Our analysis shows evidence to support the newest IDSA guidelines that patients with elevated temperatures should have a clinical workup of all alternative etiologies prior to testing for a urinary source unless the clinical suspicion is high. This will help reduce the rate of unnecessary urine cultures, the over-diagnosis of asymptomatic bacteriuria, and the overuse of antibiotics. Based on our current findings, all potential sources of fever should be ruled out prior to obtaining urinalysis, and catheters should be removed as soon as they are not needed. Urinalysis with reflex to urine culture should be reserved for those cases where there remains a high index of clinical suspicion for a urinary source.
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http://dx.doi.org/10.7759/cureus.5494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6816532PMC
August 2019

The Use of Computed Tomography Perfusion on Admission to Predict Outcomes in Surgical and Nonsurgical Traumatic Brain Injury Patients.

Cureus 2019 Jul 4;11(7):e5077. Epub 2019 Jul 4.

Neurosurgery, Riverside University Health System Medical Center, Moreno Valley, USA.

Introduction: The objective of this study was to investigate if data obtained from a computed tomography (CT) perfusion study on admission could correlate to outcomes for the patient, including the patient's length of stay in the hospital and their initial and final Glasgow Coma Scale (GCS), as well as the modified Rankin Scale (mRS) on discharge. We present an initial subset of patients fulfilling the inclusion criteria: over the age of 18 with mild, moderate, or severe traumatic brain injury (TBI). Patients admitted with a diagnosis of TBI had CT perfusion studies performed within 48 hours of admission. GCS, length of stay, mRS, and discharge location were tracked, along with the patient's course of hospitalization. Initial results and discussion on the utility of CT perfusion for predicting outcomes are presented.

Methods: Patients exhibiting mild, moderate, or severe TBI were assessed using CT perfusion within 48 hours of admission from January to July 2019 at the Arrowhead Regional Medical Center (ARMC). The neurosurgery census and patient records were assessed for progression of outcomes. Data obtained from the perfusion scans were correlated to patient outcomes to evaluate the utility of CT perfusion in predicting outcomes in surgical and nonsurgical TBI patients.

Results: Preliminary data were obtained on six patients exhibiting TBI, ranging from mild to severe. The mean GCS of our patient cohort on admission was eight, with the most common mechanism of injury found to be falls (50%) and motor vehicle accidents (50%). Cerebral blood volume (CBV) seemed to increase with Rankin value (Pearson's correlations coefficient = 0.43 but was statistically insignificant (P = 0.21)). Cerebral blood flow (CBF) was found to be correlated with CBV, and both increased with Rankin score (Pearson's correlation coefficient = 0.56) but were statistically insignificant (P = 0.27). These results suggest that with a larger sample size, CBV and CBF may be correlated to patient outcome.

Conclusion: Although more data is needed, preliminary results suggest that with larger patient populations, CT perfusion may provide information that can be correlated clinically to patient outcomes. This study shows that CBF and CBV may serve as useful indicators for prognostication of TBI patients.
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http://dx.doi.org/10.7759/cureus.5077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721926PMC
July 2019

Superior Sagittal Sinus: A Review of the History, Surgical Considerations, and Pathology.

Cureus 2019 May 3;11(5):e4597. Epub 2019 May 3.

Neurosurgery, Riverside University Health System Medical Center, Moreno Valley, USA.

A systematic PubMed and Google Scholar search for studies related to the anatomy, history, surgical approaches, complications, and diseases of the superior sagittal sinus was performed. The purpose of this review is to elucidate some of the more recent advances of our understanding of this structure. One of the earliest anatomical landmarks to be described, the superior sagittal sinus (SSS, sinus sagittalis superior (Latin); "sagittalis" Latin for 'arrow' and "sinus" Latin for 'recess, bend, or bay') has been defined and redefined by the likes of Vesalius and Cushing. A review of the various methods of approaching pathology of the SSS is discussed, as well as the historical discovery of these methods. Disease states that were emphasized include invasion of the SSS by meningioma, as well as thrombosis and vascular malformations.
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http://dx.doi.org/10.7759/cureus.4597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609282PMC
May 2019

Carbon Monoxide Poisoning: The Great Imitator.

Spartan Med Res J 2017 Aug 24;2(1):6343. Epub 2017 Aug 24.

Beaumont Hospital Southshore Campus, Trenton, MI. Michigan State University Department of Neurology & Ophthalmology, East Lansing MI.

Carbon Monoxide (CO) is one of the leading causes of poison deaths in the United States. Signs and symptoms are clinically variable secondary to inconsistent targeting of highly metabolic tissues by the gas. We report a case of a man in his early to mid-30's presenting to the emergency department with mental status changes, fatigue, headache, and flu-like symptoms for three days. The patient had been working on his motor vehicles in the garage during this time, using a portable diesel powered space heater to keep warm. Subsequent neurology and cardiology workup demonstrated bilateral globus pallidus (GP) lesions on brain imaging, increased non-myocardial infarction troponin levels, carboxyhemoglobin (COHb) level of 3.8%, elevated liver enzymes, and acute kidney failure. In this setting of his delayed presentation as a smoker with carbon monoxide poisoning, carboxyhemoglobin levels alone become less reliable. This report investigates the use of bilateral GP lesions, the most frequently affected structure, as well as damage preference to highly metabolic tissues to assist in diagnosis and prognosis for CO poisoning. Our observations can be used for further study of the relationship between bilateral GP necrosis and initial presentation and outcome of patients experiencing CO poisoning leading to earlier recognition, treatment, and decreased morbidity/mortality.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746039PMC
August 2017