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1.
Cureus ; 16(5): e61454, 2024 May.
Article in English | MEDLINE | ID: mdl-38947664

ABSTRACT

The cortical bone trajectory (CBT) technique has emerged as a minimally invasive approach for lumbar fusion but may result in pseudoarthrosis and hardware failure. This report presents a case of successful pedicle screw revision in a patient with previous failed L2 and L3 fusion using a novel "two-step" technique, including (1) drilling a new trajectory with Medtronic EM800N Stealth MIDAS Navigated MR8 drill system (Medtronic, Dublin, Ireland) and (2) placement of Solera 4.75 ATS (awl-tapped screws) with navigated POWEREASE™ (Medtronic), described here for the first time. This method involves utilizing neuronavigation and specialized instruments to safely place pedicle screws through the path of the old cortical screw trajectory, addressing the challenges associated with CBT hardware failure.

2.
Int J Mol Sci ; 24(13)2023 Jun 21.
Article in English | MEDLINE | ID: mdl-37445633

ABSTRACT

Gliomas are the most common brain tumor in adults, and molecularly targeted therapies to treat gliomas are becoming a frequent topic of investigation. The current state of molecular targeted therapy research for adult-type diffuse gliomas has yet to be characterized, particularly following the 2021 WHO guideline changes for classifying gliomas using molecular subtypes. This systematic review sought to characterize the current state of molecular target therapy research for adult-type diffuse glioma to better inform scientific progress and guide next steps in this field of study. A systematic review was conducted in accordance with PRISMA guidelines. Studies meeting inclusion criteria were queried for study design, subject (patients, human cell lines, mice, etc.), type of tumor studied, molecular target, respective molecular pathway, and details pertaining to the molecular targeted therapy-namely the modality, dose, and duration of treatment. A total of 350 studies met the inclusion criteria. A total of 52 of these were clinical studies, 190 were laboratory studies investigating existing molecular therapies, and 108 were laboratory studies investigating new molecular targets. Further, a total of 119 ongoing clinical trials are also underway, per a detailed query on clinicaltrials.gov. GBM was the predominant tumor studied in both ongoing and published clinical studies as well as in laboratory analyses. A few studies mentioned IDH-mutant astrocytomas or oligodendrogliomas. The most common molecular targets in published clinical studies and clinical trials were protein kinase pathways, followed by microenvironmental targets, immunotherapy, and cell cycle/apoptosis pathways. The most common molecular targets in laboratory studies were also protein kinase pathways; however, cell cycle/apoptosis pathways were the next most frequent target, followed by microenvironmental targets, then immunotherapy pathways, with the wnt/ß-catenin pathway arising in the cohort of novel targets. In this systematic review, we examined the current evidence on molecular targeted therapy for adult-type diffuse glioma and discussed its implications for clinical practice and future research. Ultimately, published research falls broadly into three categories-clinical studies, laboratory testing of existing therapies, and laboratory identification of novel targets-and heavily centers on GBM rather than IDH-mutant astrocytoma or oligodendroglioma. Ongoing clinical trials are numerous in this area of research as well and follow a similar pattern in tumor type and targeted pathways as published clinical studies. The most common molecular targets in all study types were protein kinase pathways. Microenvironmental targets were more numerous in clinical studies, whereas cell cycle/apoptosis were more numerous in laboratory studies. Immunotherapy pathways are on the rise in all study types, and the wnt/ß-catenin pathway is increasingly identified as a novel target.


Subject(s)
Brain Neoplasms , Glioma , Oligodendroglioma , Adult , Humans , Animals , Mice , Molecular Targeted Therapy , beta Catenin , Mutation , Glioma/drug therapy , Glioma/genetics , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Isocitrate Dehydrogenase/genetics
3.
J Neurosurg Case Lessons ; 2(8): CASE21281, 2021 Aug 23.
Article in English | MEDLINE | ID: mdl-35855087

ABSTRACT

BACKGROUND: Myeloid sarcoma is a rare malignant hematopoietic neoplasm that arises at extramedullary sites. Although myeloid sarcoma may involve any organ, central nervous system (CNS) involvement is exceptionally rare. To date, few case reports and case series have described CNS myeloid sarcoma, the majority of which include peripheral disease. OBSERVATIONS: The authors present an illustrative case of an adult male with acute myeloid leukemia (AML) in remission relapsing with an isolated, diffuse myeloid sarcoma of the cerebellum. Magnetic resonance imaging showed posterior fossa crowding and diffuse enhancement within the cerebellar white matter without an apparent mass lesion. The patient required ventriculostomy due to obstructive hydrocephalus and ultimately suboccipital craniectomy with duraplasty due to posterior fossa compression. An open cerebellar biopsy revealed myeloid sarcoma. Peripheral studies did not meet the criteria for recurrent AML. The patient subsequently received high-dose systemic chemotherapy and has responded well to treatment. LESSONS: Myeloid sarcoma may be a neurosurgical lesion because it has the potential to cause mass effect with obstructive hydrocephalus requiring emergent cerebrospinal fluid diversion and possible decompression. The authors report a rare case of isolated recurrence of AML in the form of diffuse CNS myeloid sarcoma and describe the role of neurosurgery in its diagnosis and treatment.

4.
Healthcare (Basel) ; 8(4)2020 Dec 01.
Article in English | MEDLINE | ID: mdl-33271871

ABSTRACT

The debate surrounding the integration of value in healthcare delivery and reimbursement reform has centered around integrating quality metrics into the current fee-for-service relative value units (RVU) payment model. Although a great amount of literature has been published on the creation and utilization of the RVU, there remains a dearth of information on how clinicians from various specialties view RVU and the quality-of-care metric in the compensation formula. The aim of this review is to analyze and consolidate existing theories on the RVU payment model in neurosurgery. Google and PubMed were searched for English-language literature describing opinions on the RVU in neurosurgery. Commentary was noted to be primary opinions if it was mentioned at least twice in the eight articles included in this review. Overall, seven primary opinions on the RVU were identified across the analyzed articles. Integration of quality into the RVU is viewed favorably by neurosurgeons with a few caveats and opportunities for further improvement.

5.
J Exp Neurosci ; 13: 1179069518824125, 2019.
Article in English | MEDLINE | ID: mdl-30675103

ABSTRACT

OBJECTIVE: There is a plethora of theories about the pathophysiology behind a sport-related concussion. In this review of the literature, the authors evaluated studies on the pathophysiology of sport-related concussion and professional athlete return-to-play guidelines. The goal of this article is to summarize the most common hypotheses for sport-related concussion, evaluate if there are common underlying mechanisms, and determine if correlations are seen between published mechanisms and the most current return-to-play recommendations. METHODS: Two authors selected papers from the past 5 years for literature review involving discussion of sport-related concussion and pathophysiology, pathology, or physiology of concussion using mutually agreed-upon search criteria. After the articles were filtered based on search criteria, pathophysiological explanations for concussion were organized into tables. Following analysis of pathophysiology, concussion protocols and return-to-play guidelines were obtained via a Google search for the major professional sports leagues and synthesized into a summary table. RESULTS: Out of 1112 initially identified publications, 53 met our criteria for qualitative analysis. The 53 studies revealed 5 primary neuropathological explanations for sport-related concussion, regardless of the many theories talked about in the different papers. These 5 explanations, in order of predominance in the articles analyzed, were (1) tauopathy, (2) white matter changes, (3) neural connectivity alterations, (4) reduction in cerebral perfusion, and (5) gray matter atrophy. Pathology may be sport specific: white matter changes are seen in 47% of football reports, tauopathy is seen in 50% of hockey reports, and soccer reports 50% tauopathy as well as 50% neural connectivity alterations. Analysis of the return-to-play guidelines across professional sports indicated commonalities in concussion management despite individual policies. CONCLUSIONS: Current evidence on pathophysiology for sport-related concussion does not yet support one unifying mechanism, but published hypotheses may potentially be simplified into 5 primary groups. The unification of the complex, likely multifactorial mechanisms for sport-related concussion to a few common explanations, combined with unique findings within individual sports presented in this report, may help filter and link concussion pathophysiology in sport. By doing so, the authors hope that this review will help guide future concussion research, treatment, and management.

6.
J Clin Med ; 7(4)2018 Apr 17.
Article in English | MEDLINE | ID: mdl-29673199

ABSTRACT

OBJECT: Utilization of pedicle screws (PS) for spine stabilization is common in spinal surgery. With reliance on visual inspection of anatomical landmarks prior to screw placement, the free-hand technique requires a high level of surgeon skill and precision. Three-dimensional (3D), computer-assisted virtual neuronavigation improves the precision of PS placement and minimization steps. METHODS: Twenty-three patients with degenerative, traumatic, or neoplastic pathologies received treatment via a novel three-step PS technique that utilizes a navigated power driver in combination with virtual screw technology. (1) Following visualization of neuroanatomy using intraoperative CT, a navigated 3-mm match stick drill bit was inserted at an anatomical entry point with a screen projection showing a virtual screw. (2) A Navigated Stryker Cordless Driver with an appropriate tap was used to access the vertebral body through a pedicle with a screen projection again showing a virtual screw. (3) A Navigated Stryker Cordless Driver with an actual screw was used with a screen projection showing the same virtual screw. One hundred and forty-four consecutive screws were inserted using this three-step, navigated driver, virtual screw technique. RESULTS: Only 1 screw needed intraoperative revision after insertion using the three-step, navigated driver, virtual PS technique. This amounts to a 0.69% revision rate. One hundred percent of patients had intraoperative CT reconstructed images taken to confirm hardware placement. CONCLUSIONS: Pedicle screw placement utilizing the Stryker-Ziehm neuronavigation virtual screw technology with a three step, navigated power drill technique is safe and effective.

7.
Brain Sci ; 8(1)2018 Jan 07.
Article in English | MEDLINE | ID: mdl-29316662

ABSTRACT

The authors present a unique case of recurrent stroke, discovered to be secondary to hemorrhagic conversion of microemboli from a mechanical aortic valve despite anticoagulation with Coumadin. The complexity of this case was magnified by the patient's young age, a mechanical heart valve (MHV), and a need for anticoagulation to maintain MHV patency in a setting of potentially life-threatening intracranial hemorrhage. Anticoagulant and antiplatelet therapy are risk factors for hemorrhagic conversion post-cerebral ischemia; however, the pathophysiology underlying endothelial cell dysfunction causing red blood cell extravasation is an active area of basic and clinical research. The need for randomized clinical trials to aid in the creation of standardized treatment protocol continues to go unmet. Consequently, there is marked variation in therapeutic approaches to treating intracranial hemorrhage in patients with an MHV. Unfortunately, patients with an MHV are considered at high thromboembolic (TE) risk, and these patients are often excluded from clinical trials of acute stroke due to their increased TE potential. The authors feel this case represents an example of endothelial dysfunction secondary to microthrombotic events originating from an MHV, which caused ischemic stroke with hemorrhagic conversion complicated by the need for anticoagulation for an MHV. This case offers a definitive treatment algorithm for a complex clinical dilemma.

8.
Spine (Phila Pa 1976) ; 42(5): 336-344, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28245207

ABSTRACT

STUDY DESIGN: Bibliometric analysis. OBJECTIVE: To apply the established technique of citation analysis to identify the 100 most influential articles in scoliosis surgery research published between 1900 and 2015. SUMMARY OF BACKGROUND DATA: Previous studies have applied the technique of citation analysis to other areas of study. This is the first article to apply this technique to the field of scoliosis surgery. METHODS: A two-step search of the Thomson Reuters Web of Science was conducted to identify all articles relevant to the field of scoliosis surgery. The top 100 articles with the most citations were identified based on analysis of titles and abstracts. Further statistical analysis was conducted to determine whether measures of author reputation and overall publication influence affected the rate at which publications were recognized and incorporated by other researchers in the field. RESULTS: Total citations for the final 100 publications included in the list ranged from 82 to 509. The period for publication ranged from 1954 to 2010. Most studies were published in the journal Spine (n = 63). The most frequently published topics of study were surgical techniques (n = 35) and outcomes (n = 35). Measures of author reputation (number of total studies in the top 100, number of first-author studies in the top 100) were found to have no effect on the rate at which studies were adopted by other researchers (number of years until first citation, and number of years until maximum citations). The number of citations/year a publication received was found to be negatively correlated with the rate at which it was adopted by other researchers, indicating that more influential manuscripts attained more rapid recognition by the scientific community at large. CONCLUSION: In assembling this publication, we have strived to identify and recognize the 100 most influential articles in scoliosis surgery research from 1900 to 2015. LEVEL OF EVIDENCE: N/A.


Subject(s)
Publications , Publishing , Research Personnel , Scoliosis/surgery , Spine/surgery , Bibliometrics , Humans
9.
J Clin Neurosci ; 42: 28-42, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28351533

ABSTRACT

The study of intracranial aneurysms has grown at an astounding rate since Sir Charles Symond's association of hemorrhage within the subarachnoid space to intracranial aneurysms in 1923. These associations led to the first surgical treatment of an intracranial aneurysm with wrapping by Norman Dott in 1931, and shortly thereafter, clip ligation by Walter Dandy in 1938. Surgical outcomes were improved by the introduction of the operative microscope in the 1960s and perioperative care utilizing induced hypertension, hypovolemia, and hemodilution ("HHH therapy"). Recent monumental advancements, such as coil embolization in 1990 by Guglielmi, have continued to advance the field forward. The authors hope to highlight some of the most seminal and influential works. Herein, we utilize the technique of citation analysis to assemble a list of the 100 most influential works pertaining to aneurysmal subarachnoid hemorrhage published between the years 1900 and 2015 to honor these individuals and to provide guidance to current and future researchers in the field. We additionally calculate the effects of author, journal, topic, and study design on the overall influence of publications in this field.


Subject(s)
Bibliometrics , Embolization, Therapeutic/methods , Intracranial Aneurysm/therapy , Subarachnoid Hemorrhage/therapy , Embolization, Therapeutic/adverse effects , Embolization, Therapeutic/instrumentation , Humans , Intracranial Aneurysm/pathology , Periodicals as Topic/statistics & numerical data , Subarachnoid Hemorrhage/pathology
10.
Surg Neurol Int ; 5: 4, 2014.
Article in English | MEDLINE | ID: mdl-24575319

ABSTRACT

BACKGROUND: The authors present a case to illustrate the necessity and technical feasibility of C7 laminar screw placement for treatment of sub-axial cervical spondylitic myelopathy. The indications for C7 lateral mass screw placement was required internal fixation, with small lateral masses (8 mm) and pedicles (4 mm). CASE DESCRIPTION: A 67-year-old female with compressive myelopathy after a fall from standing is presented. Magnetic resonance (MR) imaging of the cervical spine showed severe C3-6 spondylosis with canal and foraminal compromise. Computed tomography of the cervical spine confirmed the MR imaging findings as well as showed suboptimal lateral mass and pedicles for screw placement. The patient underwent a C3-6 laminectomy, C3-6 lateral mass, and C7 laminar screw placement. Postoperatively, the patient recovered without complication. CONCLUSION: Internal fixation of the cervical spine after iatrogenic destabilization by decompression of neural elements secondary to advanced spondylosis can be technically challenging. Anatomical landmarks needed for safe placement of lateral mass or pedicle instrumentation are often distorted by the patients' advanced pathology or Inherent biology. The C7 screw is a key structural element to a long construct and therefore necessitates large lateral masses or pedicles to safely place a functional screw. C7 laminar screws may be placed safely without fluoroscopic guidance when sufficient C7 lateral mass or pedicle screws are not possible or with undue risk.

11.
J Clin Neurosci ; 21(1): 148-52, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24211142

ABSTRACT

Technological advancement within the field of neuroendovascular therapy may lead to safer and more robust treatment options for patients with lesions traditionally not favorable to coil occlusion. We analyze and report our outcomes with the Orbit Galaxy Detachable Coil System (DePuy Synthes, West Chester, PA, USA) for the treatment of anterior and posterior circulation saccular cerebral aneurysms. Patients treated with Orbit Galaxy coils for primary or recurrent saccular cerebral aneurysms from October 2010 to July 2012 were retrospectively reviewed using medical records, operative reports, and radiographs. Ninety-three patients, 69% unruptured and 31% ruptured, were treated with Orbit Galaxy coils for their anterior (80%) or posterior (20%) circulation saccular cerebral aneurysm. Primary treatment with Orbit Galaxy coils occurred in 84% of patients with an initial 100% occlusion rate of 65% while 16% had Galaxy coils placed into a "secondary" recurrent lesion. The overall incidence of recurrence was 26% with a mean interval of 7 months. Retreatment for recurrence was needed in 20 patients (22%). The mortality rate was 0%. A 2% incidence of rebleed was observed; each was after a secondary treatment. The morbidity of the treatment was low with 1% having a modified Rankin score greater than 3. Primary endovascular treatment of saccular cerebral aneurysms of the anterior and posterior circulation with the Orbit Galaxy Detachable Coil System is safe and effective in the short term.


Subject(s)
Endovascular Procedures/instrumentation , Intracranial Aneurysm/surgery , Neuroendoscopy/instrumentation , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
13.
Brain Sci ; 3(1): 215-38, 2013 Mar 07.
Article in English | MEDLINE | ID: mdl-23667741

ABSTRACT

We studied a model of hemorrhagic encephalopathy of prematurity (EP) that closely recapitulates findings in humans with hemorrhagic EP. This model involves tandem insults of 20 min intrauterine ischemia (IUI) plus an episode of elevated venous pressure induced by intraperitoneal glycerol on post-natal day (P) 0. We examined Sur1 expression, which is upregulated after focal ischemia but has not been studied after brief global ischemia including IUI. We found that 20 min IUI resulted in robust upregulation of Sur1 in periventricular microvessels and tissues. We studied tandem insult pups from untreated or vehicle-treated dams (TI-CTR), and tandem insult pups from dams administered a low-dose, non-hypoglycemogenic infusion of the Sur1 blocker, glibenclamide, for 1 week after IUI (TI-GLIB). Compared to pups from the TI-CTR group, pups from the TI-GLIB group had significantly fewer and less severe hemorrhages on P1, performed significantly better on the beam walk and accelerating Rotarod on P35 and in tests of thigmotaxis and rapid learning on P35-49, and had significantly greater body and brain weights at P52. We conclude that low-dose glibenclamide administered to the mother at the end of pregnancy protects pups subjected to IUI from post-natal events of elevated venous pressure and its consequences.

14.
J Neurosurg ; 118(1): 74-83, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23082882

ABSTRACT

OBJECT: The object of this study was to assess outcomes in patients with arteriovenous malformations (AVMs) treated by Gamma Knife stereotactic radiosurgery (SRS); lesions were stratified by size, symptomatology, and Spetzler-Martin (S-M) grade. METHODS: The authors performed a retrospective analysis of 102 patients treated for an AVM with single-dose or staged-dose SRS between 1993 and 2004. Lesions were grouped by S-M grade, as hemorrhagic or nonhemorrhagic, and as small (< 3 cm) or large (≥ 3 cm). Outcomes included death, morbidity (new neurological deficit, new-onset seizure, or hemorrhage/rehemorrhage), nidus obliteration, and Karnofsky Performance Scale score. RESULTS: The mean follow-up was 8.5 years (range 5-16 years). Overall nidus obliteration (achieved in 75% of patients) and morbidity (19%) correlated with lesion size and S-M grade. For S-M Grade I-III AVMs, nonhemorrhagic and hemorrhagic combined, treatment yielded obliteration rates of 100%, 89%, and 86%, respectively; high functional status (Karnofsky Performance Scale Score ≥ 80); and 1% mortality. For S-M Grade IV and V AVMs, outcomes were less favorable, with obliteration rates of 54% and 0%, respectively. The AVMs that were not obliterated had a mean reduction in nidus volume of 69% (range 35%-96%). On long-term follow-up, 10% of patients experienced hemorrhage/rehemorrhage (6% mortality rate), which correlated with lesion size and S-M grade; the mean interval to hemorrhage was 81 months. CONCLUSIONS: For patients with S-M Grade I-III AVMs, SRS offers outcomes that are favorable and that, except for the timing of obliteration, appear to be comparable to surgical outcomes reported for the same S-M grades. Staged-dose SRS results in lesion obliteration in half of patients with S-M Grade IV lesions.


Subject(s)
Brain/surgery , Intracranial Arteriovenous Malformations/surgery , Radiosurgery/instrumentation , Adult , Female , Follow-Up Studies , Humans , Male , Retrospective Studies , Treatment Outcome
15.
J Neurosurg ; 118(3): 505-9, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23240698

ABSTRACT

OBJECT: Patients requiring neurosurgical intervention are known to be at increased risk for deep vein thrombosis (DVT) and attendant morbidity and mortality. Pulmonary embolism (PE) is the most catastrophic sequela of DVT and is the direct cause of death in 16% of all in-hospital mortalities. Protocols for DVT screening and early detection, as well as treatment paradigms to prevent PE in the acute postoperative period, are needed in neurosurgery. The authors analyzed the effectiveness of weekly lower-extremity venous duplex ultrasonography (LEVDU) in patients requiring surgical intervention for cranial or spinal pathology for detection of DVT and prevention of PE. METHODS: Data obtained in 1277 consecutive patients admitted to a major tertiary care center requiring neurosurgical intervention were retrospectively reviewed. All patients underwent admission (within 1 week of neurosurgical intervention) LEVDU as well as weekly LEVDU surveillance if the initial study was normal. Additional LEVDU was ordered in any patient in whom DVT was suspected on daily clinical physical examination or in patients in whom chest CT angiography confirmed a pulmonary embolus. An electronic database was created and statistical analyses performed. RESULTS: The overall incidence of acute DVT was 2.8% (36 patients). Of these cases of DVT, a statistically significant greater number (86%) were discovered on admission (within 1-7 days after admission) screening LEVDU (p < 0.05), whereas fewer were documented 8-14 days after admission (2.8%) or after 14 days (11.2%) postadmission. Additionally, for acute DVT detection in the present population, there were no underlying statistically significant risk factors regarding baseline physical examination, age, ambulatory status, or type of surgery. The overall incidence of acute symptomatic PE was 0.3% and the mortality rate was 0%. CONCLUSIONS: Performed within 1 week of admission in patients who will undergo neurosurgical intervention, LEVDU is effective in screening for acute DVT and initiating treatment to prevent PE, thereby decreasing the overall mortality rate. Routine LEVDU beyond this time point may not be needed to detect DVT and prevent PE unless a change in the patient's physical examination status is detected.


Subject(s)
Lower Extremity/diagnostic imaging , Neurosurgical Procedures/adverse effects , Ultrasonography, Doppler, Duplex , Venous Thrombosis/diagnostic imaging , Adult , Aged , Aged, 80 and over , Anticoagulants/administration & dosage , Female , Humans , Male , Middle Aged , Population Surveillance/methods , Retrospective Studies , Venous Thrombosis/etiology , Venous Thrombosis/prevention & control
16.
Biomed Res Int ; 2013: 715170, 2013.
Article in English | MEDLINE | ID: mdl-24490169

ABSTRACT

BACKGROUND AND PURPOSE: The Solitaire Flow Restoration was approved by the FDA in 2012 for mechanical thrombolysis of proximal occlusion of intracranial arteries. To compare the Solitaire FR device and the Merci/Penumbra (previously FDA approved) systems in terms of safety, clinical outcomes, and efficacy including radiographic brain parenchymal salvage. METHODS: Thirty-one consecutive patients treated with the Solitaire and 20 patients with comparable baseline characteristics treated with Merci or Penumbra systems were included in the study. Primary outcome measures included recanalization rate and modified Rankin Scale score at followup. Secondary outcomes included length of procedure, incidence of symptomatic intracranial hemorrhage, 90-day mortality, and radiographic analysis of percentage area salvage. RESULTS: Compared with the Merci/Penumbra group, the Solitaire group showed a statistically significant improvement in favorable outcomes (mRS ≤ 2) (69% versus 35%, P = 0.03) and symptomatic ICH rate (0 versus 15%, P = 0.05) with a trend towards higher recanalization rates (93.5% versus 75%, P = 0.096) and shorter length of procedure (58.5 min versus 70.8 min, P = 0.08). Radiographic comparison also showed a significantly larger area of salvage in the Solitaire group (81.9% versus 71.9%, P = 0.05). CONCLUSION: Our study suggests that the Solitaire system allows faster, safer, and more efficient thrombectomy than Merci or Penumbra systems.


Subject(s)
Stroke/therapy , Thrombolytic Therapy/methods , Treatment Outcome , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Radiography , Stroke/diagnostic imaging , Stroke/epidemiology , Stroke/physiopathology , United States
17.
J Neurosurg Pediatr ; 8(6): 628-39, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22132923

ABSTRACT

OBJECT: Encephalopathy of prematurity (EP) is common in preterm, low birth weight infants who require postnatal mechanical ventilation. The worst types of EP are the hemorrhagic forms, including choroid plexus, germinal matrix, periventricular, and intraventricular hemorrhages. Survivors exhibit life-long cognitive, behavioral, and motor abnormalities. Available preclinical models do not fully recapitulate the salient features of hemorrhagic EP encountered in humans. In this study, the authors evaluated a novel model using rats that featured tandem insults of transient prenatal intrauterine ischemia (IUI) plus transient postnatal raised intrathoracic pressure (RIP). METHODS: Timed-pregnant Wistar rats were anesthetized and underwent laparotomy on embryonic Day 19. Intrauterine ischemia was induced by clamping the uterine and ovarian vasculature for 20 minutes. Natural birth occurred on embryonic Day 22. Six hours after birth, the pups were subjected to an episode of RIP, induced by injecting glycerol (50%, 13 µl/g intraperitoneally). Control groups included naive, sham surgery, and IUI alone. Pathological, histological, and behavioral analyses were performed on pups up to postnatal Day 52. RESULTS: Compared with controls, pups subjected to IUI+RIP exhibited significant increases in postnatal mortality and hemorrhages in the choroid plexus, germinal matrix, and periventricular tissues as well as intraventricularly. On postnatal Days 35-52, they exhibited significant abnormalities involving complex vestibulomotor function and rapid spatial learning. On postnatal Day 52, the brain and body mass were significantly reduced. CONCLUSIONS: Tandem insults of IUI plus postnatal RIP recapitulate many features of the hemorrhagic forms of EP found in humans, suggesting that these insults in combination may play important roles in pathogenesis.


Subject(s)
Animals, Newborn/injuries , Brain Diseases , Disease Models, Animal , Infant, Premature, Diseases , Animals , Female , Gestational Age , Glycerol/pharmacology , Humans , Infant, Newborn , Ischemia/physiopathology , Ligation/methods , Pregnancy , Prenatal Injuries/physiopathology , Pressure , Rats , Rats, Wistar , Solvents/pharmacology , Thorax/drug effects , Thorax/physiopathology , Uterus/blood supply
18.
Neurosurg Focus ; 25(5): E9, 2008.
Article in English | MEDLINE | ID: mdl-18980483

ABSTRACT

Traumatic central cord syndrome (TCCS), regardless of its biomechanics, is the most frequently encountered incomplete spinal cord injury. Patients with TCCS present with disproportionate weakness of the upper extremities, and variable sensory loss and bladder dysfunction. Fractures and/or subluxations, forced hyperextension, and herniated nucleus pulposus are the main pathogenetic mechanisms of TCCS. Nearly 50% of patients with TCCS suffer from congenital or degenerative spinal stenosis and sustained their injuries during hyperextension as originally described by Schneider in 1954. Immunohistochemical and imaging studies indicate mild to moderate insult to axons and their ensheathing myelin in the lateral funiculi culminating in cytoskeletal injury and impaired conduction. More than one-half of these patients enjoy spontaneous recovery of motor weakness; however, as time goes on, lack of manual dexterity, neuropathic pain, spasticity, bladder dysfunction, and imbalance of gait render their activities of daily living nearly impossible. Based on the current level of evidence, there is no clear indication of the timing of decompression for relief of sustained spinal cord compression in hyperextension injuries. Future research, taking advantage of validated digital imaging data such as maximum canal compromise, maximum spinal cord compression, and lesion length on the CT and MR images, as well as more sensitive measures of bladder and hand function, spasticity, and neuropathic pain may help tailor surgery for a specific group of these patients.


Subject(s)
Central Cord Syndrome/etiology , Cervical Vertebrae/injuries , Spinal Cord Injuries/complications , Age Factors , Animals , Central Cord Syndrome/pathology , Central Cord Syndrome/therapy , Humans , Magnetic Resonance Imaging , Spinal Cord Injuries/pathology , Spinal Cord Injuries/therapy
19.
Pediatr Res ; 64(6): 648-52, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18679166

ABSTRACT

Germinal matrix (GM) hemorrhage (GMH) is a major cause of mortality and of life-long morbidity from cerebral palsy. GMH is typically preceded by hypoxic/ischemic events and is believed to arise from rupture of weakened veins in the GM. In the CNS, hypoxia/ischemia up-regulate sulfonylurea receptor 1 (SUR1)-regulated NCCa-ATP channels in microvascular endothelium, with channel activation by depletion of ATP being responsible for progressive secondary hemorrhage. We hypothesized that this channel might be up-regulated in the GM of preterm infants at risk for GMH. Here, we studied expression of the regulatory subunit of the channel, SUR1, and its transcriptional antecedent, hypoxia inducible factor 1 (HIF1), in postmortem tissues of premature infants who either were at risk for or who sustained GMH. We found regionally specific up-regulation of HIF1 and of SUR1 protein and mRNA in GM tissues, compared with remote cortical tissues. Up-regulation was prominent in most progenitor cells, whereas in veins, SUR1 was found predominantly in infants who had sustained GMH compared with those without hemorrhage. Our data suggest that the SUR1-regulated NCCa-ATP channel may be associated with GMH, and that pharmacological block of these channels could potentially reduce the incidence of this devastating complication of prematurity.


Subject(s)
ATP-Binding Cassette Transporters/metabolism , Cerebral Hemorrhage/physiopathology , Hypoxia-Inducible Factor 1/metabolism , Infant, Premature , Potassium Channels, Inwardly Rectifying/metabolism , Receptors, Drug/metabolism , ATP-Binding Cassette Transporters/genetics , Animals , Brain/blood supply , Brain/metabolism , Brain/pathology , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/mortality , Cerebral Hemorrhage/pathology , Cerebral Palsy/etiology , Cerebral Palsy/pathology , Humans , Hypoxia-Inducible Factor 1/genetics , Infant, Newborn , Potassium Channels, Inwardly Rectifying/genetics , Premature Birth , Receptors, Drug/genetics , Sulfonylurea Receptors
20.
Epilepsy Behav ; 5(5): 768-71, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15380133

ABSTRACT

Vagus nerve stimulation (VNS) is an important therapeutic option for individuals with refractory epilepsy who have failed multiple antiepileptic drugs (AEDs). The intricate relationship of the vagus nerve to cardiac function raises concern that vagal stimulation may affect cardiac rhythm and function. Previous pre- and postmarketing studies have not shown this to be a significant problem, with the incidence of bradyarrhythmias reported to be about 0.1%. We review three cases of ventricular asystole with complete heart block that occurred during intraoperative lead tests. The purpose of these case reports is to identify the specific type of cardiac abnormality associated with vagus nerve stimulation and to identify individuals at risk.


Subject(s)
Electric Stimulation Therapy/adverse effects , Epilepsy/complications , Epilepsy/therapy , Heart Arrest/etiology , Heart Block/etiology , Vagus Nerve/physiology , Adult , Anticonvulsants/therapeutic use , Diabetes Complications , Drug Resistance , Electric Stimulation Therapy/instrumentation , Electrodes, Implanted , Humans , Hypertension/complications , Male
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