Publications by authors named "Osama Kashlan"

29 Publications

  • Page 1 of 1

Safety and Efficacy of 23.4% Sodium Chloride Administered via Peripheral Venous Access for the Treatment of Cerebral Herniation and Intracranial Pressure Elevation.

Neurocrit Care 2021 Jun 25. Epub 2021 Jun 25.

Department of Neurosurgery, University of Michigan, 3552 Taubman Health Care Center, SPC 5338, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA.

Background: Sodium chloride (NaCl) 23.4% solution has been shown to reduce intracranial pressure (ICP) and reverse transtentorial herniation. A limitation of 23.4% NaCl is its high osmolarity (8008 mOsm/l) and the concern for tissue injury or necrosis following extravasation when administered via peripheral venous access. The use of this agent is therefore often limited to central venous or intraosseous routes of administration. Our objective was to evaluate the safety and efficacy of administration of 23.4% NaCl via peripheral venous access compared with administration via central venous access.

Methods: We reviewed pharmacy records to identify all administrations of 23.4% NaCl at our institution between December 2017 and February 2020. Medical records were then reviewed to identify complications, such as extravasation, soft tissue injury or necrosis, hypotension (mean arterial pressure less than 65 mm Hg), pulmonary edema, hemolysis, and osmotic demyelination. We also compared the change in physiological variables, such as ICP, mean arterial pressure, cerebral perfusion pressure, and heart rate, as well as laboratory values, such as sodium, chloride, bicarbonate, creatinine, and hemoglobin, following administration of 23.4% NaCl via the peripheral and central venous routes.

Results: We identified 299 administrations of 23.4% NaCl (242 central and 57 peripheral) in 141 patients during the study period. There was no documented occurrence of soft tissue injury or necrosis in any patient. One patient developed hypotension following central administration. Among the 38 patients with ICP monitoring at the time of drug administration, there was no significant difference in median ICP reduction (- 13 mm Hg [central] vs. - 24 mm Hg [peripheral], p = 0.21) or cerebral perfusion pressure augmentation (16 mm Hg [central] vs. 15 mm Hg [peripheral], p = 0.87) based on route of administration.

Conclusions: Peripheral venous administration of 23.4% NaCl is safe and achieves a reduction in ICP equivalent to that achieved by administration via central venous access.
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http://dx.doi.org/10.1007/s12028-021-01248-7DOI Listing
June 2021

Navigation and Robotic-Assisted Single-Position Prone Lateral Lumbar Interbody Fusion: Technique, Feasibility, Safety, and Case Series.

World Neurosurg 2021 08 29;152:221-230.e1. Epub 2021 May 29.

Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA. Electronic address:

Background: Single-position prone lateral interbody fusion is a recently introduced technical modification of the minimally invasive retroperitoneal transpsoas approach for lateral lumbar interbody fusion (LLIF). Several technical descriptions of single-position prone LLIF have been published with traditional fluoroscopy for guidance. However, there has been no investigation of either three-dimensional computed tomography-based navigation for prone LLIF or integration with robotic assistance platforms with the prone lateral technique. This study evaluated the feasibility and safety of spinal navigation and robotic assistance for single-position prone LLIF.

Methods: Retrospective review of medical records and a prospectively acquired database for a single center was performed to examine immediate and 30-day clinical and radiographic outcomes for consecutive patients undergoing single-position prone LLIF with spinal navigation and/or robotic assistance.

Results: Nine patients were treated, 4 women and 5 men. Mean age was 65.4 years (range, 46-75 years), and body mass index was 30.2 kg/m (range, 24-38 kg/m). The most common surgical indication was adjacent segment disease (44.4%), followed by pseudarthrosis (22.2%), spondylolisthesis (11.1%), degenerative disc disease (11.1%), and recurrent stenosis (11.1%). Postoperative approach-related complications included pain-limited bilateral hip flexor weakness (4/5) and pain-limited left knee extension weakness (4/5) in 1 patient (11.1%) and right lateral thigh numbness and dysesthesia in 1 patient (11.1%). All cages were placed within quarters 2-3, signifying the middle portion of the disc space. There were no instances of misguidance by navigation.

Conclusions: Integration of spinal navigation and robotic assistance appears feasible, accurate, and safe as an alternative to fluoroscopic guidance for single-position LLIF.
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http://dx.doi.org/10.1016/j.wneu.2021.05.097DOI Listing
August 2021

Safety Profile and Radiographic and Clinical Outcomes of Stand-Alone 2-Level Anterior Lumbar Interbody Fusion: A Case Series of 41 Consecutive Patients.

Cureus 2020 Nov 24;12(11):e11684. Epub 2020 Nov 24.

Neurosurgery, Emory University School of Medicine, Atlanta, USA.

Objective: The use of stand-alone 2-level anterior lumbar interbody fusion (ALIF) for degenerative lumbar disease has been increasing as an alternative to routinely augmenting these constructs with posterior fixation or fusion. Despite the potential benefits of a stand-alone approach (decreased cost and operative time, decreased pain and early mobilization), there is a paucity of information regarding these operations in the literature. This investigation aimed to determine the safety profile, radiographic outcomes including fusion rates, improvement in preoperative pain, and spinopelvic parameter modification, for patients undergoing stand-alone 2-level ALIF.

Methods: This retrospective case series involved a chart review of all patients undergoing 2-level stand-alone ALIF at a single tertiary hospital from 2008 to 2018. Data included patient demographics, hospitalization, complications and radiological studies. Visual analog scale (VAS) back and leg scores were measured via patient-administered surveys preoperatively and up to 18 weeks postoperatively.

Results: Forty-one patients who underwent L4-S1 stand-alone ALIF were included. Sixteen (39%) of patients had undergone previous posterior lumbar surgery. Length of stay averaged 4.2 days. Complication rates were comparable to 1-level ALIF. Two patients required reoperation. Fusion rates were 100% for L4-5 and 94.4% for L5-S1. There was no significant change in lumbar lordosis (LL) or LL-pelvic incidence (PI), but there was improved segmental lordosis (SL) and disc height at L4-S1 on final follow-up imaging. There was also modest but statistically significant improvement in VAS back and leg scores.

Conclusions: Stand-alone 2-level ALIF is an option for a surgeon to perform in the absence of significant instability, even in the setting of prior posterior surgery. These procedures increase SL and disc height, but do not have the same effect on LL or LL-PI.
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http://dx.doi.org/10.7759/cureus.11684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769802PMC
November 2020

Impact of Michigan's new opioid prescribing laws on spine surgery patients: analysis of the Michigan Spine Surgery Improvement Collaborative.

J Neurosurg Spine 2020 Dec 11:1-6. Epub 2020 Dec 11.

Departments of1Neurosurgery and.

Objective: In 2017, Michigan passed new legislation designed to reduce opioid abuse. This study evaluated the impact of these new restrictive laws on preoperative narcotic use, short-term outcomes, and readmission rates after spinal surgery.

Methods: Patient data from 1 year before and 1 year after initiation of the new opioid laws (beginning July 1, 2018) were queried from the Michigan Spine Surgery Improvement Collaborative database. Before and after implementation of the major elements of the new laws, 12,325 and 11,988 patients, respectively, were treated.

Results: Patients before and after passage of the opioid laws had generally similar demographic and surgical characteristics. Notably, after passage of the opioid laws, the number of patients taking daily narcotics preoperatively decreased from 3783 (48.7%) to 2698 (39.7%; p < 0.0001). Three months postoperatively, there were no differences in minimum clinically important difference (56.0% vs 58.0%, p = 0.1068), numeric rating scale (NRS) score of back pain (3.5 vs 3.4, p = 0.1156), NRS score of leg pain (2.7 vs 2.7, p = 0.3595), satisfaction (84.4% vs 84.7%, p = 0.6852), or 90-day readmission rate (5.8% vs 6.2%, p = 0.3202) between groups. Although there was no difference in readmission rates, pain as a reason for readmission was marginally more common (0.86% vs 1.22%, p = 0.0323).

Conclusions: There was a meaningful decrease in preoperative narcotic use, but notably there was no apparent negative impact on postoperative recovery, patient satisfaction, or short-term outcomes after spinal surgery despite more restrictive opioid prescribing. Although the readmission rate did not significantly increase, pain as a reason for readmission was marginally more frequently observed.
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http://dx.doi.org/10.3171/2020.7.SPINE20729DOI Listing
December 2020

The feasibility of computer-assisted 3D navigation in multiple-level lateral lumbar interbody fusion in combination with posterior instrumentation for adult spinal deformity.

Neurosurg Focus 2020 09;49(3):E4

Objective: The lateral lumbar interbody fusion (LLIF) technique is used to treat many common spinal degenerative pathologies including kyphoscoliosis. The use of spinal navigation for LLIF has not been broadly adopted, especially in adult spinal deformity. The purpose of this study was to evaluate the feasibility as well as the intraoperative and navigation-related complications of computer-assisted 3D navigation (CaN) during multiple-level LLIF for spinal deformity.

Methods: Retrospective analysis of clinical and operative characteristics was performed for all patients > 18 years of age who underwent multiple-level CaN LLIF combined with posterior instrumentation for adult spinal deformity at the University of Michigan between 2014 and 2020. Intraoperative CaN-related complications, LLIF approach-related postoperative complications, and medical postoperative complications were assessed.

Results: Fifty-nine patients were identified. The mean age was 66.3 years (range 42-83 years) and body mass index was 27.6 kg/m2 (range 18-43 kg/m2). The average coronal Cobb angle was 26.8° (range 3.6°-67.0°) and sagittal vertical axis was 6.3 cm (range -2.3 to 14.7 cm). The average number of LLIF and posterior instrumentation levels were 2.97 cages (range 2-5 cages) and 5.78 levels (range 3-14 levels), respectively. A total of 6 intraoperative complications related to the LLIF stage occurred in 5 patients. Three of these were CaN-related and occurred in 2 patients (3.4%), including 1 misplaced lateral interbody cage (0.6% of 175 total lateral cages placed) requiring intraoperative revision. No patient required a return to the operating room for a misplaced interbody cage. A total of 12 intraoperative complications related to the posterior stage occurred in 11 patients, with 5 being CaN-related and occurring in 4 patients (6.8%). Univariate and multivariate analyses revealed no statistically significant risk factors for intraoperative and CaN-related complications. Transient hip weakness and numbness were found to be in 20.3% and 22.0% of patients, respectively. At the 1-month follow-up, weakness was observed in 3.4% and numbness in 11.9% of patients.

Conclusions: Use of CaN in multiple-level LLIF in the treatment of adult spinal deformity appears to be a safe and effective technique. The incidence of approach-related complications with CaN was 3.4% and cage placement accuracy was high.
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http://dx.doi.org/10.3171/2020.5.FOCUS20353DOI Listing
September 2020

The impact of age on approach-related complications with navigated lateral lumbar interbody fusion.

Neurosurg Focus 2020 09;49(3):E8

Objective: Age is known to be a risk factor for increased complications due to surgery. However, elderly patients can gain significant quality-of-life benefits from surgery. Lateral lumbar interbody fusion (LLIF) is a minimally invasive procedure that is commonly used to treat degenerative spine disease. Recently, 3D navigation has been applied to LLIF. The purpose of this study was to determine whether there is an increased complication risk in the elderly with navigated LLIF.

Methods: Patients who underwent 3D-navigated LLIF for degenerative disease from 2014 to 2019 were included in the analysis. Patients were divided into elderly and nonelderly groups, with those 65 years and older categorized as elderly. Ninety-day medical and surgical complications were recorded. Patient and surgical characteristics were compared between groups, and multivariate regression analysis was used to determine independent risk factors for complication.

Results: Of the 115 patients included, 56 were elderly and 59 were nonelderly. There were 15 complications (25.4%) in the nonelderly group and 10 (17.9%) in the elderly group, which was not significantly different (p = 0.44). On multivariable analysis, age was not a risk factor for complication (p = 0.52). However, multiple-level LLIF was associated with an increased risk of approach-related complication (OR 3.58, p = 0.02).

Conclusions: Elderly patients do not appear to experience higher rates of approach-related complications compared with nonelderly patients undergoing 3D navigated LLIF. Rather, multilevel surgery is a predictor for approach-related complication.
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http://dx.doi.org/10.3171/2020.6.FOCUS20311DOI Listing
September 2020

Magnetic resonance imaging of human neural stem cells in rodent and primate brain.

Stem Cells Transl Med 2021 Jan 25;10(1):83-97. Epub 2020 Aug 25.

Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.

Stem cell transplantation therapies are currently under investigation for central nervous system disorders. Although preclinical models show benefit, clinical translation is somewhat limited by the absence of reliable noninvasive methods to confirm targeting and monitor transplanted cells in vivo. Here, we assess a novel magnetic resonance imaging (MRI) contrast agent derived from magnetotactic bacteria, magneto-endosymbionts (MEs), as a translatable methodology for in vivo tracking of stem cells after intracranial transplantation. We show that ME labeling provides robust MRI contrast without impairment of cell viability or other important therapeutic features. Labeled cells were visualized immediately post-transplantation and over time by serial MRI in nonhuman primate and mouse brain. Postmortem tissue analysis confirmed on-target grft location, and linear correlations were observed between MRI signal, cell engraftment, and tissue ME levels, suggesting that MEs may be useful for determining graft survival or rejection. Overall, these findings indicate that MEs are an effective tool for in vivo tracking and monitoring of cell transplantation therapies with potential relevance to many cellular therapy applications.
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http://dx.doi.org/10.1002/sctm.20-0126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780819PMC
January 2021

Effect of Fenestrated Pedicle Screws with Cement Augmentation in Osteoporotic Patients Undergoing Spinal Fusion.

World Neurosurg 2020 11 7;143:e351-e361. Epub 2020 Aug 7.

Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA. Electronic address:

Objective: Osteoporosis is a well-known risk factor for instrumentation failure and subsequent pseudoarthrosis after spinal fusion. In the present systematic review, we analyzed the biomechanical properties, clinical efficacy, and complications of cement augmentation via fenestrated pedicle screws in spinal fusion.

Methods: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Reports appearing in the PubMed database up to March 31, 2020 were queried using the key words "cement," "pedicle screw," and "osteoporosis." We excluded non-English language studies, studies reported before 2000, studies that had involved use of cement without fenestrated pedicle screws, nonhuman studies, technical reports, and individual case reports.

Results: Twenty-five studies met the inclusion criteria. Eleven studies had tested the biomechanics of cement-augmented fenestrated pedicle screws. The magnitude of improvement achieved by cement augmentation of pedicle screws increased with the degree of osteoporosis. The cement-augmented fenestrated pedicle screw was superior biomechanically to the alternative "solid-fill" technique. Fourteen studies had evaluated complications. Cement extravasation with fenestrated screw usage was highly variable, ranging from 0% to 79.7%. However, cement extravasation was largely asymptomatic. Thirteen studies had assessed the outcomes. The use of cement-augmented fenestrated pedicles decreased screw pull out and improved fusion rates; however, the clinical outcomes were similar to those with traditional pedicle screw placement.

Conclusions: The use of cement-augmented fenestrated pedicle screws can be an effective strategy for achieving improved pedicle screw fixation in patients with osteoporosis. A potential risk is cement extravasation; however, this complication will typically be asymptomatic. Larger comparative studies are needed to better delineate the clinical efficacy.
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http://dx.doi.org/10.1016/j.wneu.2020.07.154DOI Listing
November 2020

Patients with a depressive and/or anxiety disorder can achieve optimum Long term outcomes after surgery for grade 1 spondylolisthesis: Analysis from the quality outcomes database (QOD).

Clin Neurol Neurosurg 2020 10 17;197:106098. Epub 2020 Jul 17.

Department of Neurologic Surgery, University of Michigan, Ann Arbor, Michigan, United States.

Introduction: In the current study, we sought to compare baseline demographic, clinical, and operative characteristics, as well as baseline and follow-up patient reported outcomes (PROs) of patients with any depressive and/or anxiety disorder undergoing surgery for low-grade spondylolisthesis using a national spine registry.

Patients And Methods: The Quality Outcomes Database (QOD) was queried for patients undergoing surgery for Meyerding grade 1 lumbar spondylolisthesis undergoing 1-2 level decompression or 1 level fusion at 12 sites with the highest number of patients enrolled in QOD with 2-year follow-up data.

Results: Of the 608 patients identified, 25.6 % (n = 156) had any depressive and/or anxiety disorder. Patients with a depressive/anxiety disorder were less likely to be discharged home (p < 0.001). At 3=months, patients with a depressive/anxiety disorder had higher back pain (p < 0.001), lower quality of life (p < 0.001) and higher disability (p = 0.013); at 2 year patients with depression and/or anxiety had lower quality of life compared to those without (p < 0.001). On multivariable regression, depression was associated with significantly lower odds of achieving 20 % or less ODI (OR 0.44, 95 % CI 0.21-0.94,p = 0.03). Presence of an anxiety disorder was not associated with decreased odds of achieving that milestone at 3 months. The presence of depressive-disorder, anxiety-disorder or both did not have an impact on ODI at 2 years. Finally, patient satisfaction at 2-years did not differ between the two groups (79.8 % vs 82.7 %,p = 0.503).

Conclusion: We found that presence of a depressive-disorder may impact short-term outcomes among patients undergoing surgery for low grade spondylolisthesis but longer term outcomes are not affected by either a depressive or anxiety disorder.
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http://dx.doi.org/10.1016/j.clineuro.2020.106098DOI Listing
October 2020

Correlation Between the Oswestry Disability Index and the North American Spine Surgery Patient Satisfaction Index.

World Neurosurg 2020 07 25;139:e724-e729. Epub 2020 Apr 25.

Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA. Electronic address:

Background: The Oswestry Disability Index (ODI) is a widely used patient-reported outcome instrument in lumbar spine surgery, but its relationship to the increasingly scrutinized but still heterogeneous patient satisfaction metrics has not been well described. One popular metric is the North American Spine Society (NASS) patient satisfaction index. This study aimed to determine whether change in ODI predicts patient satisfaction.

Methods: Adult patients at a neurosurgery spine clinic completed the ODI and NASS questionnaires at various times in their care between September 2014 and November 2018. Scores were retrospectively analyzed using ordinal logistic regression.

Results: One thousand thirty-seven patients were identified (mean age 59.3 ± 14.7 years, 54.2% male). At 3, 12, and 24 months postoperatively, 684 (84.5%), 400 (83.3%), and 215 (80.9%) patients, respectively, expressed satisfaction (NASS score 1 or 2). Mean ± standard deviation improvements in ODI at 3, 12, and 24 months postoperatively were 16.8 ± 17.5 (n = 675), 18.4 ± 17.5 (n = 396), and 19.7 ± 17.7 (n = 213). For every unit improvement in ODI, the odds of selecting the next most satisfied NASS score at 3, 12, and 24 months postoperatively increased by 6.8% (95% confidence interval [CI] 5.6%-8.1%), 5.8% (95% CI 4.4%-7.1%), and 6.0% (95% CI 4.2%-7.9%), respectively. Every 10-unit improvement increased the odds, respectively, by 93.8% (95% CI 73.2%-117.0%), 75.0% (95% CI 53.8%-99.1%), and 79.4% (95% CI 50.3%-114.1%).

Conclusions: Improvements in ODI are predictive of increased patient satisfaction as defined by the NASS index. A 10-point improvement in ODI nearly doubled the odds of increased satisfaction 3 months postoperatively.
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http://dx.doi.org/10.1016/j.wneu.2020.04.117DOI Listing
July 2020

Advantages of the Combination of Conscious Sedation Epidural Anesthesia Under Fluoroscopy Guidance in Lumbar Spine Surgery.

J Pain Res 2020 21;13:211-219. Epub 2020 Jan 21.

Department of Neurosurgery, Nanoori Hospital Bupyeong, Incheon, Republic of Korea.

Background: With the increase in life expectancy seen throughout the world, the prevalence of degenerative spinal pathology and surgery to treat it has increased. Spinal surgery under general anesthesia leads to various problems and complications, especially in patients with numerous medical comorbidities or elderly patients. For this reason, there is a need for safer anesthetic methods applicable to unhealthy, elderly patients undergoing spinal surgery.

Purpose: To report our experience with utilizing fluoroscopy-guided epidural anesthesia in conjunction with conscious sedation in spinal surgery.

Patients And Methods: We performed a retrospective review of 111 patients at our institution that received fluoroscopy-guided epidural anesthesia for lumbar surgery from February to September 2018. Patients' records were evaluated to evaluate patient demographics, American Society of Anesthesiology Physical Classification System (ASA) class, and pain numerical rating scores (NRS) preoperatively and throughout their recovery postoperatively. Intraoperative data including volume of epidural anesthetic used, extent of epidural spread, and inadvertent subdural injection was collected. Postoperative recovery time was also collected.

Results: The mean age of our patients was 60 years old with a range between 31 and 83 years old. All patients experienced decreases in postoperative pain with no significant differences based on age or ASA class. There was no association between ASA class and time to recovery postoperatively. Older patients (age 70 years or greater) had a significantly longer recovery time when compared to younger patients. Recovery also was longer for patients who received higher volumes of epidural anesthesia. For every 1 mL increase of epidural anesthetic given, there was an increase in the extent of spread of 1.8 spinal levels.

Conclusion: We demonstrate the safety and feasibility of utilizing conscious sedation in conjunction with fluoroscopy-guided epidural anesthesia in the lumbar spinal surgery.
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http://dx.doi.org/10.2147/JPR.S227212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982434PMC
January 2020

Predictors of surgical treatment in children with tethered fibrofatty filum terminale.

J Neurosurg Pediatr 2019 Nov 1:1-8. Epub 2019 Nov 1.

1Department of Neurosurgery, University of Michigan.

Objective: Thickened or fatty filum terminale is an occult lesion that can cause tethered cord syndrome requiring surgical untethering. This study's objectives were to estimate the incidence of tethered fibrofatty filum terminale (TFFT) in a large insured pediatric population, identify predictors of surgery among those TFFT patients, and assess a diagnostic algorithm.

Methods: TFFT was defined according to the ICD-9-CM code for cord tethering (742.59), after excluding codes for diastematomyelia, lipomyelomeningocele, terminal myelocystocele, meningocele, and myelomeningocele. Utilizing the Optum Insight database for 2001-2014, the authors identified pediatric patients (< 21 years) in the US who were diagnosed with a tethered cord and estimated the TFFT incidence rates in that source population and the surgical untethering probability among TFFT patients over the 14-year period. Logistic regression was used to estimate the effects (adjusted OR and 95% CI) of age at diagnosis, sex, Charlson Comorbidity Index (CCI) score, diagnosis of Chiari malformation type I, diagnosis of syrinx, and the probability of surgery by US census region. Lastly, to evaluate their algorithm for identifying TFFT from ICD-9 codes, the authors estimated its positive predictive value (PPV) among 50 children who were diagnosed at their institution and met the ICD-9-CM criteria.

Results: There were 3218 diagnoses of TFFT, with 482 of these pediatric patients undergoing tethered cord release during the study period. The estimated incidence rate was 12.0 per 100,000/year (95% CI 11.6-12.4 per 100,000/year). The incidence rate was slightly higher in females than in males (12.7 vs 11.4 per 100,000/year). The probability of surgery in the total pediatric TFFT population was 15.0% (95% CI 13.8%-16.2%) and was greater in children with a syrinx (OR 2.2, 95% CI 1.6-3.0), children 7-11 years of age at diagnosis versus < 1 year (OR 1.5, 95% CI 1.1-2.0), CCI score ≥ 3 versus 0 (OR 2.3, 95% CI 1.4-3.8), and residents of the Western vs Northeastern US (OR 2.3, 95% CI 1.6-3.5). In the authors' own institution's database, the PPV of TFFT was 35/50 (70.0%, 95% CI 57.3%-82.7%) for identifying tethered cord due to fibrofatty filum terminale among childhood positives.

Conclusions: Patients with comorbidities or an associated syrinx showed a higher risk of untethering procedures for TFFT. Also, surgery was appreciably more frequent in the Western US. These findings signify the need for a collaborative prospective cohort study of long-term outcomes for TFFT patients with and without surgery to determine which patients should have surgery.
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http://dx.doi.org/10.3171/2019.8.PEDS19292DOI Listing
November 2019

Evolution of Spinal Endoscopic Surgery.

Neurospine 2019 Mar 31;16(1):6-14. Epub 2019 Mar 31.

Department of Neurosurgery, Nanoori Incheon Hospital, Incheon, Korea.

Innovations in the development of endoscopic spinal surgery were classified into different generations and reviewed. Future developments and directions for endoscopic spinal surgery were discussed. Surgical therapy for spinal disease has been gradually changing from traditional open surgery to minimally invasive spinal surgery. Recently, endoscopic spinal surgery, which initially was limited to the treatment of soft tissue lesions, has expanded to include other aspects of spinal disease and good clinical results have been reported. As the paradigm of spinal surgery shifts from open surgery to endoscopic surgery, we discussed the evolution of endoscopic spine surgery in our literature review. Through this description, we presented possibilities of future developments and directions in endoscopic spine surgery.
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http://dx.doi.org/10.14245/ns.1836322.161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449828PMC
March 2019

X-rays and scans can fail to differentiate hip pathology from lumbar spinal stenosis: Two case reports.

Surg Neurol Int 2019 23;10:165. Epub 2019 Aug 23.

Departments of Neurosurgery Nanoori Hospital, Seoul, Republic of Korea.

Background: Occasionally, hip pathologies may present alone or combined with lumbar spine pathology, especially lumbar stenosis. Although the history and clinical examination may help differentiate between the two, hip X-rays alone without accompanying magnetic resonance imaging (MRI) studies may prove unreliable.

Case Descriptions: Case 1 - A 72-year-old male presented with the sudden onset of severe back and left posterior thigh pain. Straight leg raising test was positive at 70° (right) and 60° (left), and he had left lower extremity numbness and weakness. The lumbar MRI showed L5-S1 spinal stenosis. Although X-rays of both hips were negative, the MRI showed bilateral femoral neck fractures. He underwent screw fixation of the hip fractures and later underwent endoscopic decompression of the spinal stenosis. Case 2 - A 35-year-old male presented with low backache and right hip pain of 1 month's duration. The neurological examination was normal, except for positive straight leg raising bilaterally at 60°. The spine MRI was normal. However, despite negative X-ray of both hips, the hip MRI revealed avascular necrosis (AVN) of both femoral heads requiring subsequent orthopedic management.

Conclusion: Hip pathology may mimic lumbar spinal stenosis. In the two cases presented, plain X-rays failed to document hip fractures (case 1) and AVN (case 2), respectively, both of which were later diagnosed on MRI studies.
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http://dx.doi.org/10.25259/SNI_173_2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763674PMC
August 2019

Percutaneous Endoscopic Contralateral Lumbar Foraminal Decompression via an Interlaminar Approach: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown) 2020 Apr;18(4):E118-E119

Department of Neurosurgery, Nanoori Incheon Hospital, Incheon, Republic of Korea.

Nerve root compression by foraminal pathology is challenging for a surgeon to decompress without violating the facet joint, which may necessitate a fusion procedure. One nonfusion approach to foraminal pathology is a combination intracanal approach for a laminotomy/foraminotomy followed by a paraspinal Wiltse approach for far lateral decompression. Unfortunately, even with the combination approach, it continues to be difficult to achieve adequate decompression without violating much of the facet joint overlying the nerve root. Spine endoscopy offers the ability to decompress the foraminal portion of the nerve without significant violation of the facet joint. We present a surgical video describing the technique for performing a percutaneous endoscopic contralateral L5-S1 foraminal decompression via an interlaminar approach, for a patient presenting with a left L5 radiculopathy due to L5-S1 foraminal stenosis. We explain the differences in the endoscopic channel docking point between ipsilateral and contralateral interlaminar approaches. The steps of an endoscopic foraminotomy are then described: dissect soft tissue and ligamentum flavum off the medial left S1 lamina and superior articulating process (SAP), undercut the superior articulating process of S1 and the inferior articulating process (IAP) of L5 with a drill, resect lateral ligamentum flavum off SAP and IAP exposing epidural fat, and finally dissect the left L5 nerve root and remove compressive lesions throughout its course in the lateral recess, foramen, and laterally. The presentation ends with an intraoperative photograph showing a decompressed L5 nerve root and postoperative imaging confirming this decompression. Appropriate patient consent was obtained.
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http://dx.doi.org/10.1093/ons/opz162DOI Listing
April 2020

Percutaneous Transforaminal Endoscopic Radiofrequency Ablation of the Sinuvertebral Nerve in an Olympian with a Left L5 Pedicle/Pars Interarticularis Fracture-Associated Left L5-S1 Disk Desiccation.

World Neurosurg X 2019 Jul 13;3:100032. Epub 2019 Mar 13.

Department of Neurosurgery, Nanoori Hospital, Incheon, Republic of Korea.

Background: Irritation of the sinuvertebral nerve by a posterior or posterolateral disk desiccation can cause somatic referred pain that can mimic a lumbar radiculopathy. We present a case of a patient presenting with this condition and the positive result in pain improvement after endoscopic radiofrequency ablation of the sinuvertebral nerve.

Case Description: An 18-year-old Olympic runner presented to our clinic with back pain and left leg pain in a clear L5 distribution. He did not have a history of trauma. His imaging did not demonstrate any lesion causing compression of the left L5 nerve root as expected. He was found to have a left healing L5 pedicle fracture and ipsilateral chronic L5 pars interarticularis fracture. He was also found to have an ipsilateral minor left L5-S1 disk desiccation. His visual analog scale (VAS) score was 7. After a positive provocative diskogram, the patient underwent percutaneous transforaminal endoscopic radiofrequency ablation of the left L5 sinuvertebral nerve, which was irritated by the left L5-S1 disk desiccation. At his 6-month follow-up visit, the patient's VAS score was 1.

Conclusions: It is important for clinicians to remember that back-associated leg pain can be caused by somatic referred pain because of irritation of the sinuvertebral nerve. Endoscopic radiofrequency of this nerve can be beneficial in pain control, but further randomized prospective trials are needed to study these techniques further.
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http://dx.doi.org/10.1016/j.wnsx.2019.100032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584597PMC
July 2019

Radiographic outcomes of endoscopic decompression for lumbar spinal stenosis.

Neurosurg Focus 2019 05;46(5):E10

1Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan; and.

OBJECTIVELumbar central stenosis can theoretically be decompressed with minimal bone removal via an endoscopic approach. Although multiple studies have demonstrated an adequate radiographic decompression, none has quantified the volume of bone removal after endoscopic decompression. The objective of this study was to quantify the 3D volume of bone removed from the lamina and facet joints during endoscopic decompression for lumbar central and lateral recess stenosis.METHODSThis retrospective study included adults with lumbar spinal stenosis who underwent endoscopic decompression of a single level or 2 noncontiguous lumbar levels. Central stenosis on MRI was graded preoperatively and postoperatively using the Schizas scale. A computer program was developed in MATLAB to semiautomatically perform a 3D volumetric analysis of preoperative and postoperative lumbar CT scans. The volumetric percentage of bone removed from the lamina and facet joints ipsilateral and contralateral to the side of approach was quantified.RESULTSNineteen patients with 21 treated lumbar levels were included in the study. Preoperatively, the number of levels with Schizas stenosis grades B, C, and D were 5, 12, and 4, respectively. Stenosis grades improved postoperatively to grades A, B, C, and D for 17, 3, 1, and 0 levels, respectively. All levels improved by at least 1 stenosis grade. The volumetric percentage of laminar bone removed was 15.5% (95% CI 11.2%-19.8%, p < 0.001) from the ipsilateral lamina and 8.8% (95% CI 5.7%-11.8%, p < 0.001) from the contralateral lamina. The percentage of facet joint resection was 5.3% (95% CI 4.2%-6.4%, p < 0.001) and 4.3% (95% CI 2.2%-6.4%, p < 0.001) for the ipsilateral and contralateral facet joints, respectively. Average pain scores, as measured by the visual analog scale, improved from 7.9 preoperatively to 2.2 by 3-10 months postoperatively (p < 0.001).CONCLUSIONSEndoscopic lumbar decompression achieves improvement in the radiographic grade of lumbar central stenosis with minimal bone removal from the lamina and facet joints. Future prospective studies are needed to validate the findings of this study with more comprehensive clinical outcomes.
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http://dx.doi.org/10.3171/2019.2.FOCUS18617DOI Listing
May 2019

Percutaneous Endoscopic Transforaminal Approach for Far Lateral Lumbar Discectomy: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown) 2020 Jan;18(1):E8

Department of Neurosurgery, Nanoori Incheon Hospital, Incheon, Republic of Korea.

The conventional surgical approach to far lateral lumbar disk herniations is a paraspinal Wiltse approach. During the Wiltse approach, it is sometimes necessary to resect some of the facet or pars interarticularis to achieve an adequate exposure. The endoscopic transforaminal route can be of benefit in far lateral disk herniations due to direct access to the epidural space through Kambin's triangle, without the need for any bony removal or nerve retraction. In this video, we describe a percutaneous endoscopic transforaminal approach for far lateral discectomy in a patient presenting with a left L4 radiculopathy due to a far lateral L4-5 disk herniation. We describe Kambin's triangle anatomy and its relevance to the transforaminal route. The steps of the procedure are then described: dissection of soft tissue and removal of free disk fragments on the inferior aspect of the foramen far from the compressed exiting nerve route above to decrease the risk of retraction injury, gentle maneuvering of endoscope superiorly with removal of further compressive disk fragments, exposure of the exiting nerve root superiorly after adequate decompression is achieved and removal of any remaining fragments in close proximity to the nerve, and finally evaluation of traversing nerve root for any compressive lesions. The presentation ends with postoperative imaging confirming decompression of the far lateral disk herniation.
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http://dx.doi.org/10.1093/ons/opz037DOI Listing
January 2020

The Use of Anterior Lumbosacral Interbody Fusion in Spinopelvic Stabilization After High Partial Sacrectomy.

Oper Neurosurg (Hagerstown) 2019 10;17(4):E173-E176

Department of Neurosurgery, Emory University, Atlanta, Georgia.

Background And Importance: Traditionally, when a patient presents with a midline chordoma with extension to the mid-S1 body where neither S1 nerve roots can be spared, the recommendation would be to perform a total sacrectomy for en bloc resection. This procedure, however, results in a large bony defect that makes it difficult to achieve fusion across the lumbosacral and sacroiliac junction (SIJ). To help prevent this challenge in the situation described above, we propose performing a high sacrectomy for en bloc resection with placement of an anterior L5-S1 graft instead in specific situations where the tumor extends to the mid-S1 body leaving the superior aspect of S1 unaffected.

Clinical Presentation: A 56-yr-old female presented to our clinic with back pain, leg pain, urinary incontinence, and perineal numbness. She was found to have a chordoma that extended to the mid-S1 body superiorly. Her S1 nerve roots were involved extraforaminally. We performed the operation described above with no signs of hardware malfunction or tumor recurrence at 5 mo.

Conclusion: In patients where the sacral tumor that involves the S1 nerve roots but does not involve the superior portion of the S1 body, there continues to be unaffected SIJ to allow for arthrodesis, and an anterior approach is necessary for other indications, we recommend performing a high partial sacrectomy with placement of an anterior L5-S1 graft rather than a total sacrectomy as long as the bony resection offers ability to obtain tumor margins.
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http://dx.doi.org/10.1093/ons/opy377DOI Listing
October 2019

Targeted intraspinal injections to assess therapies in rodent models of neurological disorders.

Nat Protoc 2019 02;14(2):331-349

Department of Neurology, University of Michigan, Ann Arbor, MI, USA.

Despite decades of research, pharmacological therapies for spinal cord motor pathologies are limited. Alternatives using macromolecular, viral, or cell-based therapies show early promise. However, introducing these substances into the spinal cord, past the blood-brain barrier, without causing injury is challenging. We describe a technique for intraspinal injection targeting the lumbar ventral horn in rodents. This technique preserves motor performance and has a proven track record of translation into phase 1 and 2 clinical trials in amyotrophic lateral sclerosis (ALS) patients. The procedure, in brief, involves exposure of the thoracolumbar spine and dissection of paraspinous muscles over the target vertebrae. Following laminectomy, the spine is affixed to a stereotactic frame, permitting precise and reproducible injection throughout the lumbar spine. We have used this protocol to inject various stem cell types, primarily human spinal stem cells (HSSCs); however, the injection is adaptable to any candidate therapeutic cell, virus, or macromolecule product. In addition to a detailed procedure, we provide stereotactic coordinates that assist in targeting of the lumbar spine and instructional videos. The protocol takes ~2 h per animal.
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http://dx.doi.org/10.1038/s41596-018-0095-5DOI Listing
February 2019

Human neural stem cell transplantation improves cognition in a murine model of Alzheimer's disease.

Sci Rep 2018 10 3;8(1):14776. Epub 2018 Oct 3.

Department of Neurology, University of Michigan, Ann Arbor, MI, USA.

Stem cell transplantation offers a potentially transformative approach to treating neurodegenerative disorders. The safety of cellular therapies is established in multiple clinical trials, including our own in amyotrophic lateral sclerosis. To initiate similar trials in Alzheimer's disease, efficacious cell lines must be identified. Here, we completed a preclinical proof-of-concept study in the APP/PS1 murine model of Alzheimer's disease. Human neural stem cell transplantation targeted to the fimbria fornix significantly improved cognition in two hippocampal-dependent memory tasks at 4 and 16 weeks post-transplantation. While levels of synapse-related proteins and cholinergic neurons were unaffected, amyloid plaque load was significantly reduced in stem cell transplanted mice and associated with increased recruitment of activated microglia. In vitro, these same neural stem cells induced microglial activation and amyloid phagocytosis, suggesting an immunomodulatory capacity. Although long-term transplantation resulted in significant functional and pathological improvements in APP/PS1 mice, stem cells were not identified by immunohistochemistry or PCR at the study endpoint. These data suggest integration into native tissue or the idea that transient engraftment may be adequate for therapeutic efficacy, reducing the need for continued immunosuppression. Overall, our results support further preclinical development of human neural stem cells as a safe and effective therapy for Alzheimer's disease.
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http://dx.doi.org/10.1038/s41598-018-33017-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170460PMC
October 2018

Human neural stem cell transplantation into the corpus callosum of Alzheimer's mice.

Ann Clin Transl Neurol 2017 10 18;4(10):749-755. Epub 2017 Aug 18.

Department of Neurology University of Michigan Ann Arbor Michigan.

The hippocampus has been the target of stem cell transplantations in preclinical studies focused on Alzheimer's disease, with results showing improvements in histological and behavioral outcomes. The corpus callosum is another structure that is affected early in Alzheimer's disease. Therefore, we hypothesize that this structure is a novel target for human neural stem cell transplantation in transgenic Alzheimer's disease mouse models. This study demonstrates the feasibility of targeting the corpus callosum and identifies an effective immunosuppression regimen for transplanted neural stem cell survival. These results support further preclinical development of the corpus callosum as a therapeutic target in Alzheimer's disease.
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http://dx.doi.org/10.1002/acn3.443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634341PMC
October 2017

Human Cortical Neural Stem Cells Expressing Insulin-Like Growth Factor-I: A Novel Cellular Therapy for Alzheimer's Disease.

Stem Cells Transl Med 2016 Mar 7;5(3):379-91. Epub 2016 Jan 7.

Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA A. Alfred Taubman Medical Research Institute, University of Michigan, Ann Arbor, Michigan, USA

Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disorder and a leading cause of dementia. Current treatment fails to modify underlying disease pathologies and very little progress has been made to develop effective drug treatments. Cellular therapies impact disease by multiple mechanisms, providing increased efficacy compared with traditional single-target approaches. In amyotrophic lateral sclerosis, we have shown that transplanted spinal neural stem cells (NSCs) integrate into the spinal cord, form synapses with the host, improve inflammation, and reduce disease-associated pathologies. Our current goal is to develop a similar "best in class" cellular therapy for AD. Here, we characterize a novel human cortex-derived NSC line modified to express insulin-like growth factor-I (IGF-I), HK532-IGF-I. Because IGF-I promotes neurogenesis and synaptogenesis in vivo, this enhanced NSC line offers additional environmental enrichment, enhanced neuroprotection, and a multifaceted approach to treating complex AD pathologies. We show that autocrine IGF-I production does not impact the cell secretome or normal cellular functions, including proliferation, migration, or maintenance of progenitor status. However, HK532-IGF-I cells preferentially differentiate into gamma-aminobutyric acid-ergic neurons, a subtype dysregulated in AD; produce increased vascular endothelial growth factor levels; and display an increased neuroprotective capacity in vitro. We also demonstrate that HK532-IGF-I cells survive peri-hippocampal transplantation in a murine AD model and exhibit long-term persistence in targeted brain areas. In conclusion, we believe that harnessing the benefits of cellular and IGF-I therapies together will provide the optimal therapeutic benefit to patients, and our findings support further preclinical development of HK532-IGF-I cells into a disease-modifying intervention for AD.
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http://dx.doi.org/10.5966/sctm.2015-0103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807660PMC
March 2016

Histological Bulbar Manifestations in the ALS Rat.

Neurodegener Dis 2015 24;15(2):121-6. Epub 2015 Mar 24.

Department of Neurosurgery, University of Michigan, Ann Arbor, Mich., USA.

Background: Almost all patients with amyotrophic lateral sclerosis (ALS) develop bulbar symptoms; therefore, it is important to have valid animal models that accurately reflect these features. While the SOD1-G93A rat is extensively used as an ALS model, bulbar symptoms in this model are not well characterized.

Objective: In the present study, we aimed to better characterize bulbar dysfunction in terms of histology to determine whether the SOD1-G93A rat is a useful model for bulbar-onset ALS.

Methods: Sixty-day-old SOD1-G93A rats on a Sprague-Dawley background and age-matched wild-type controls were assessed weekly for global motor function, facial nerve function, and vagal nerve function. The study endpoint was determined when an SOD1-G93A rat could not right itself within 30 s of being placed on its side. At that point, neuronal counts were assessed in different brainstem cranial nerve nuclei. In addition, the masseter muscle, posterior belly of the digastric muscle, and tongue muscle were evaluated for intact neuromuscular junctions.

Results: Our data demonstrate decreases in the number of motor neurons in the trigeminal, facial, and hypoglossal nuclei, as well as compromised neuromuscular junction integrity in the muscles they innervate.

Conclusion: These findings suggest that, from a histological standpoint, the SOD1-G93A rat is a valid model of ALS bulbar symptoms.
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http://dx.doi.org/10.1159/000377725DOI Listing
January 2016

Pedicle-sparing transforaminal thoracic spine wedge osteotomy for kyphosis correction.

Surg Neurol Int 2014 30;5(Suppl 15):S561-3. Epub 2014 Dec 30.

Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.

Background: Correction of a focal kyphotic deformity at times requires performing a pedicle subtraction osteotomy, which is accompanied by loss of pedicles as anchor points at the affected level in addition to significant blood loss. To help alleviate these two issues, a novel osteotomy technique for correction of kyphosis using a transforaminal approach to the thoracic vertebral body is described.

Methods: We describe a bilateral pedicle-sparing approach and demonstrate it in a patient with proximal junctional kyphosis.

Results: The proposed osteotomy resulted in a 28-degree Cobb angle improvement in the sagittal plane.

Conclusion: The operation resulted in a similar degree of correction as a pedicle subtraction osteotomy, with the added benefit of maintaining the pedicles closest to the kyphotic deformity.
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http://dx.doi.org/10.4103/2152-7806.148041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287908PMC
January 2015

Reducing costs while maintaining quality in endovascular neurosurgical procedures.

J Neurosurg 2014 Nov 29;121(5):1071-6. Epub 2014 Aug 29.

Departments of 1 Neurosurgery and.

Object: As medical costs continue to rise during a time of increasing medical resource utilization, both hospitals and physicians must attempt to limit superfluous health care expenses. Neurointerventional treatment has been shown to be costly, but it is often the best treatment available for certain neuropathologies. The authors studied the effects of 3 policy changes designed to limit the costs of performing neurointerventional procedures at the University of Michigan.

Methods: The authors retrospectively analyzed the costs of performing neurointerventional procedures during the 6-month periods before and after the implementation of 3 cost-saving policies: 1) the use of an alternative, more economical contrast agent, 2) standardization of coil prices through negotiation with industry representatives to receive economies of scale, and 3) institution of a feedback method to show practitioners the costs of unused products per patient procedure. The costs during the 6-month time intervals before and after implementation were also compared with costs during the most recent 6-month time period.

Results: The policy requiring use of a more economical contrast agent led to a decrease in the cost of contrast usage of $42.79 per procedure for the first 6 months after implementation, and $137.09 per procedure for the most current 6-month period, resulting in an estimated total savings of $62,924.31 for the most recent 6-month period. The standardized coil pricing system led to savings of $159.21 per coil after the policy change, and $188.07 per coil in the most recent 6-month period. This yielded total estimated savings of $76,732.56 during the most recent 6-month period. The feedback system for unused items decreased the cost of wasted products by approximately $44.36 per procedure in the 6 months directly after the policy change and by $48.20 per procedure in the most recent 6-month period, leading to total estimated savings of $22,123.80 during the most recent 6-month period. According to extrapolation over a 1-year period, the 3 policy changes decreased costs by an estimated $323,561.34.

Conclusions: Simple cost-saving policies can lead to substantial reductions in costs of neurointerventional procedures while maintaining high levels of quality and growth of services.
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http://dx.doi.org/10.3171/2014.7.JNS14236DOI Listing
November 2014

Meningioangiomatosis: a case report and literature review emphasizing diverse appearance on different imaging modalities.

Case Rep Neurol Med 2011 9;2011:361203. Epub 2011 Oct 9.

Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA 30322, USA.

Purpose. Meningioangiomatosis (MA) is a rare, benign lesion that commonly mimics other intracranial malformations in clinical presentation and appearance on imaging. The case presented and the literature review performed highlight the importance of combining MRI and CT results to better characterize intracranial lesions and including MA on the list of differential diagnoses of patients presenting with seizures. Methods. The case described is of a 19-year-old male with a 10-year history of worsening seizures refractory to multiple drug regimens. MRI revealed an atypical vascular malformation. The patient underwent surgical resection of the epileptogenic cortex. Results. Although the radiologic impression of the lesion was a vascular malformation, pathological examination revealed MA. A literature search performed highlights the variability of the appearance of MA on CT and MRI and suggests the utility of the T2 GRE sequence in illustrating the presence of calcification and, in a lesion with other characteristic features, the diagnosis of MA. Conclusion. MA can be a difficult diagnosis to make based on imaging findings alone. However, in a patient with a characteristic history and presentation, the presence of a calcified mass on CT and MRI brain susceptibility artifact on a T2 GRE sequence may suggest MA.
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http://dx.doi.org/10.1155/2011/361203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3420442PMC
August 2012

Microinfusion using hollow microneedles.

Pharm Res 2006 Jan 30;23(1):104-13. Epub 2006 Nov 30.

School of Chemical and Biomolecular Engineering and Center for Drug Design, Development and Delivery, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.

Purpose: The aim of the study is to determine the effect of experimental parameters on microinfusion through hollow microneedles into skin to optimize drug delivery protocols and identify rate-limiting barriers to flow.

Methods: Glass microneedles were inserted to a depth of 720-1080 microm into human cadaver skin to microinfuse sulforhodamine solution at constant pressure. Flow rate was determined as a function of experimental parameters, such as microneedle insertion and retraction distance, infusion pressure, microneedle tip geometry, presence of hyaluronidase, and time.

Results: Single microneedles inserted into skin without retraction were able to infuse sulforhodamine solution into the skin at flow rates of 15-96 microl/h. Partial retraction of microneedles increased flow rate up to 11.6-fold. Infusion flow rate was also increased by greater insertion depth, larger infusion pressure, use of a beveled microneedle tip, and the presence of hyaluronidase such that flow rates ranging from 21 to 1130 microl/h were achieved. These effects can be explained by removing or overcoming the large flow resistance imposed by dense dermal tissue, compressed during microneedle insertion, which blocks flow from the needle tip.

Conclusions: By partially retracting microneedles after insertion and other methods to overcome flow resistance of dense dermal tissue, protocols can be designed for hollow microneedles to microinfuse fluid at therapeutically relevant rates.
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http://dx.doi.org/10.1007/s11095-005-8498-8DOI Listing
January 2006
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